Pub Date : 2022-11-10DOI: 10.3389/frabi.2022.1043302
E. M. Okon, R. Okocha, B. Adesina, Judith O. Ehigie, O. Alabi, A. M. Bolanle, N. Matekwe, B. M. Falana, A. M. Tiamiyu, I. O. Olatoye, O. Adedeji
Antimicrobial resistance (AMR) is a significant threat to global public health. Specifically, excessive usage of antimicrobials in food animal production is one significant reason for AMR development in humans. Therefore, it is essential to identify the trends of AMR in fish and poultry and develop better surveillance strategies for the future. Despite this imperative need, such information is not well documented, especially in Africa. This study used a systematic review to assess AMR trend, spatial distribution, and incidence in fish and poultry research in Nigeria, Egypt, and South Africa. A literature assessment was conducted for published studies on AMR between 1989 and 2021 using the Scopus and Web of Science databases. One hundred and seventy-three relevant articles were obtained from the database search. Egypt was the leading exponent of antimicrobial resistance research (43.35%, 75 studies), followed by Nigeria (39.31%, 68 studies), then South Africa (17.34%, 30 studies). The majority of the antimicrobial resistance studies were on poultry in Egypt (81%, 61 studies), Nigeria (87%, 59 studies), and South Africa (80%, 24 studies). Studies on fish were 17% (13 studies), 9% (6 studies), and 10% (3 studies) in Egypt, Nigeria, and South Africa, respectively. Antimicrobial resistance patterns showed multiple drug resistance and variations in resistant genes. AMR research focused on sulfamethoxazole groups, chloramphenicol, trimethoprim, tetracycline, erythromycin, and ampicillin. Most studies employed the disk diffusion method for antimicrobial susceptibility tests. Among the four mechanisms of AMR, limiting drug uptake was the most reported in this study (both in fish and poultry). The findings reveal public and environmental health threats and suggest that it would be useful to promote and advance AMR research, particularly for countries on the global hotspot for antimicrobial use.
抗微生物药物耐药性(AMR)是对全球公共卫生的重大威胁。具体而言,在食用动物生产中过度使用抗菌剂是导致人类抗菌素耐药性发展的一个重要原因。因此,必须确定鱼类和家禽中抗菌素耐药性的趋势,并为未来制定更好的监测战略。尽管有这种迫切需要,但这方面的资料没有很好的记录,特别是在非洲。本研究采用系统综述的方法评估了尼日利亚、埃及和南非鱼类和家禽研究中的AMR趋势、空间分布和发病率。使用Scopus和Web of Science数据库对1989年至2021年间发表的AMR研究进行了文献评估。从数据库检索中获得173篇相关文章。埃及是抗菌药物耐药性研究的主要国家(43.35%,75项研究),其次是尼日利亚(39.31%,68项研究),然后是南非(17.34%,30项研究)。大多数抗菌素耐药性研究发生在埃及(81%,61项研究)、尼日利亚(87%,59项研究)和南非(80%,24项研究)的家禽身上。在埃及、尼日利亚和南非,对鱼类的研究分别为17%(13项研究)、9%(6项研究)和10%(3项研究)。耐药模式显示多重耐药和耐药基因的变异。抗菌素耐药性的研究重点是磺胺甲恶唑、氯霉素、甲氧苄啶、四环素、红霉素和氨苄西林。多数研究采用纸片扩散法进行药敏试验。在抗菌素耐药性的四种机制中,限制药物摄取是本研究中报道最多的(在鱼类和家禽中)。研究结果揭示了公共和环境健康威胁,并表明促进和推进抗菌素耐药性研究将是有益的,特别是对处于抗菌素使用全球热点的国家。
{"title":"Antimicrobial resistance in fish and poultry: Public health implications for animal source food production in Nigeria, Egypt, and South Africa","authors":"E. M. Okon, R. Okocha, B. Adesina, Judith O. Ehigie, O. Alabi, A. M. Bolanle, N. Matekwe, B. M. Falana, A. M. Tiamiyu, I. O. Olatoye, O. Adedeji","doi":"10.3389/frabi.2022.1043302","DOIUrl":"https://doi.org/10.3389/frabi.2022.1043302","url":null,"abstract":"Antimicrobial resistance (AMR) is a significant threat to global public health. Specifically, excessive usage of antimicrobials in food animal production is one significant reason for AMR development in humans. Therefore, it is essential to identify the trends of AMR in fish and poultry and develop better surveillance strategies for the future. Despite this imperative need, such information is not well documented, especially in Africa. This study used a systematic review to assess AMR trend, spatial distribution, and incidence in fish and poultry research in Nigeria, Egypt, and South Africa. A literature assessment was conducted for published studies on AMR between 1989 and 2021 using the Scopus and Web of Science databases. One hundred and seventy-three relevant articles were obtained from the database search. Egypt was the leading exponent of antimicrobial resistance research (43.35%, 75 studies), followed by Nigeria (39.31%, 68 studies), then South Africa (17.34%, 30 studies). The majority of the antimicrobial resistance studies were on poultry in Egypt (81%, 61 studies), Nigeria (87%, 59 studies), and South Africa (80%, 24 studies). Studies on fish were 17% (13 studies), 9% (6 studies), and 10% (3 studies) in Egypt, Nigeria, and South Africa, respectively. Antimicrobial resistance patterns showed multiple drug resistance and variations in resistant genes. AMR research focused on sulfamethoxazole groups, chloramphenicol, trimethoprim, tetracycline, erythromycin, and ampicillin. Most studies employed the disk diffusion method for antimicrobial susceptibility tests. Among the four mechanisms of AMR, limiting drug uptake was the most reported in this study (both in fish and poultry). The findings reveal public and environmental health threats and suggest that it would be useful to promote and advance AMR research, particularly for countries on the global hotspot for antimicrobial use.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47700992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-03DOI: 10.3389/frabi.2022.1052316
G. Agga, H. Galloway, A. Netthisinghe
Enterococci are a normal flora of the gastrointestinal tracts of humans and animals. Enterococci can also cause life-threatening nosocomial infections. Antimicrobial-resistant Enterococcus species have been reported in the feedlot and dairy cattle productions and in meat and milk products, suggesting their foodborne importance. Cow-calf operations represent a significant segment in the beef production system by producing weaned calves. Weaned calves are brought into the feedlot to be finished for meat, and culled cows are also slaughtered for beef, primarily for ground beef products. Infection dynamics in the cow-calf operation can contribute to meat contamination. This study evaluated the effects of age and wheat grazing on the concentration and prevalence of a macrolide antibiotic erythromycin (ERYr) and tetracycline (TETr) resistant enterococci, associated resistance genes and species distribution in a cow-calf production system. In 2017 and 2018, 32 Angus breed cow-calf pairs were randomly assigned to feed on tall fescue or wheat pasture in two independent field experiments. During the grazing experiments of 2-3 weeks, fecal samples were collected weekly and cultured to enumerate, isolate and identify ERYr, TETr, and generic enterococci, using media supplemented with erythromycin, tetracycline or non-supplemented media, respectively. The two main species frequently associated with human illnesses, Enterococcus faecium and E. faecalis, were widely distributed in the cow-calf groups. Generic and TETr- enterococci were prevalent (96-100% prevalence) and abundant (3.2-4.9 log10 CFU/g) in the cow-calf population; however, ERYr enterococci were enumerable by direct plating only from a single cow despite being detected in at least 40% of the fecal samples after enrichment, showing their low abundance. TET- and ERY-resistance were mainly conferred by tet(M) and erm(B), respectively. Wheat grazing reduced the concentration of TETr enterococci and modified enterococcal species and resistance gene distributions. Hence, it is necessary to further investigate wheat grazing in cow-calf production as a potential strategy to mitigate antimicrobial resistance.
{"title":"Effects of age and pasture type on the concentration and prevalence of tetracycline and macrolide resistant Enterococcus species in beef cow-calf production system","authors":"G. Agga, H. Galloway, A. Netthisinghe","doi":"10.3389/frabi.2022.1052316","DOIUrl":"https://doi.org/10.3389/frabi.2022.1052316","url":null,"abstract":"Enterococci are a normal flora of the gastrointestinal tracts of humans and animals. Enterococci can also cause life-threatening nosocomial infections. Antimicrobial-resistant Enterococcus species have been reported in the feedlot and dairy cattle productions and in meat and milk products, suggesting their foodborne importance. Cow-calf operations represent a significant segment in the beef production system by producing weaned calves. Weaned calves are brought into the feedlot to be finished for meat, and culled cows are also slaughtered for beef, primarily for ground beef products. Infection dynamics in the cow-calf operation can contribute to meat contamination. This study evaluated the effects of age and wheat grazing on the concentration and prevalence of a macrolide antibiotic erythromycin (ERYr) and tetracycline (TETr) resistant enterococci, associated resistance genes and species distribution in a cow-calf production system. In 2017 and 2018, 32 Angus breed cow-calf pairs were randomly assigned to feed on tall fescue or wheat pasture in two independent field experiments. During the grazing experiments of 2-3 weeks, fecal samples were collected weekly and cultured to enumerate, isolate and identify ERYr, TETr, and generic enterococci, using media supplemented with erythromycin, tetracycline or non-supplemented media, respectively. The two main species frequently associated with human illnesses, Enterococcus faecium and E. faecalis, were widely distributed in the cow-calf groups. Generic and TETr- enterococci were prevalent (96-100% prevalence) and abundant (3.2-4.9 log10 CFU/g) in the cow-calf population; however, ERYr enterococci were enumerable by direct plating only from a single cow despite being detected in at least 40% of the fecal samples after enrichment, showing their low abundance. TET- and ERY-resistance were mainly conferred by tet(M) and erm(B), respectively. Wheat grazing reduced the concentration of TETr enterococci and modified enterococcal species and resistance gene distributions. Hence, it is necessary to further investigate wheat grazing in cow-calf production as a potential strategy to mitigate antimicrobial resistance.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44889763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-26DOI: 10.3389/frabi.2022.993271
M. Kamita, Michael Maina, R. Kimani, R. Mwangi, D. Mureithi, Cynthia Nduta, J. Gitaka
Antibiotic resistance causes higher morbidity and mortality and higher healthcare costs. One of the factors influencing the emergence of antibiotic resistance is the inappropriate use of antibiotics. Clinical practitioners’ incorrect prescription patterns and a disregard for antibiotic usage recommendations are the leading causes of this resistance. This study examined the antibiotic prescription patterns among hospitalized patients at the Kiambu Level 5 hospital (KL5) to find potential for hospital quality improvement. This study was conducted in July 2021, and all patients hospitalized on the study day were included. The information was extracted from patient medical records using a World Health Organization Point Prevalence Survey (PPS) instrument. Anonymized data was gathered, entered, and then SPSS version 26 was used for analysis. Among the 308 surveyed patients, 191 (62%) received antibiotic medication, and 60.1% of the total were female. The pediatric ward, which had an antibiotic prescription rate of 94.1%, had the highest rate of antibiotic usage, followed by the medical ward (69.2%) and gynecological ward (65.6%). Over 40% of antibiotic prescriptions had a prophylactic medical indication. Penicillin G was the most prescribed antibiotic for community-acquired infections (32.2%), followed by 3rd generation cephalosporins (27.6%) and aminoglycosides (17.2%). Based on the AWaRe classification, 57% of the prescribed antibiotics were in the Access class while 42% were in the Watch class. Incomplete site of indication, lack of a method of administration, and length of administration are some of the conformities that were missing in the medical records. This study shows that antibiotic prescription rates are high, particularly for young patients, and there is a higher risk of antibiotic misuse. The data makes a compelling justification for using antibiotic stewardship practices in Kenyan hospitals.
{"title":"Point prevalence survey to assess antibiotic prescribing pattern among hospitalized patients in a county referral hospital in Kenya","authors":"M. Kamita, Michael Maina, R. Kimani, R. Mwangi, D. Mureithi, Cynthia Nduta, J. Gitaka","doi":"10.3389/frabi.2022.993271","DOIUrl":"https://doi.org/10.3389/frabi.2022.993271","url":null,"abstract":"Antibiotic resistance causes higher morbidity and mortality and higher healthcare costs. One of the factors influencing the emergence of antibiotic resistance is the inappropriate use of antibiotics. Clinical practitioners’ incorrect prescription patterns and a disregard for antibiotic usage recommendations are the leading causes of this resistance. This study examined the antibiotic prescription patterns among hospitalized patients at the Kiambu Level 5 hospital (KL5) to find potential for hospital quality improvement. This study was conducted in July 2021, and all patients hospitalized on the study day were included. The information was extracted from patient medical records using a World Health Organization Point Prevalence Survey (PPS) instrument. Anonymized data was gathered, entered, and then SPSS version 26 was used for analysis. Among the 308 surveyed patients, 191 (62%) received antibiotic medication, and 60.1% of the total were female. The pediatric ward, which had an antibiotic prescription rate of 94.1%, had the highest rate of antibiotic usage, followed by the medical ward (69.2%) and gynecological ward (65.6%). Over 40% of antibiotic prescriptions had a prophylactic medical indication. Penicillin G was the most prescribed antibiotic for community-acquired infections (32.2%), followed by 3rd generation cephalosporins (27.6%) and aminoglycosides (17.2%). Based on the AWaRe classification, 57% of the prescribed antibiotics were in the Access class while 42% were in the Watch class. Incomplete site of indication, lack of a method of administration, and length of administration are some of the conformities that were missing in the medical records. This study shows that antibiotic prescription rates are high, particularly for young patients, and there is a higher risk of antibiotic misuse. The data makes a compelling justification for using antibiotic stewardship practices in Kenyan hospitals.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46102318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-24DOI: 10.3389/frabi.2022.1001717
René Arredondo-Hernández, C. Siebe, G. Castillo-Rojas, S. Ponce de León, Y. López-Vidal
A healthy development is denied to millions of children worldwide as harsh life conditions manifest themselves in an altered inflammation-prone microbiome crosstalk environment. Keynote of this tragedy is that insufficient nutritious amino acid blocks lipids-intake to sustain diverse microbiota, and promotes the generalist strategy followed by Escherichia coli -besides other proteobacteria- of shifting gut metabolism, subverting the site specificity of first immune reaction. Furthermore, it could be hypothesized that selective success lies in their ability to induce inflammation, since this phenomenon also fuels horizontal gene transfer (HGT). In this review, we dilucidate how immune mechanisms of environmental enteric dysfunction affect overgrowth restriction, infectious morbidity rate, and acquired lifelong risks among severe acute malnourished children. Also, despite acknowledging complexities of antimicrobial resistant enrichment, we explore and speculate over the links between virulence regulation and HGT as an indissociable part in the quest for new inflammatory niches by open genome bacteria, particularly when both collide in the most vulnerable.
{"title":"The synergistic interaction of systemic inflammation, dysbiosis and antimicrobial resistance promotes growth restriction in children with acute severe malnutrition: An emphasis on Escherichia coli","authors":"René Arredondo-Hernández, C. Siebe, G. Castillo-Rojas, S. Ponce de León, Y. López-Vidal","doi":"10.3389/frabi.2022.1001717","DOIUrl":"https://doi.org/10.3389/frabi.2022.1001717","url":null,"abstract":"A healthy development is denied to millions of children worldwide as harsh life conditions manifest themselves in an altered inflammation-prone microbiome crosstalk environment. Keynote of this tragedy is that insufficient nutritious amino acid blocks lipids-intake to sustain diverse microbiota, and promotes the generalist strategy followed by Escherichia coli -besides other proteobacteria- of shifting gut metabolism, subverting the site specificity of first immune reaction. Furthermore, it could be hypothesized that selective success lies in their ability to induce inflammation, since this phenomenon also fuels horizontal gene transfer (HGT). In this review, we dilucidate how immune mechanisms of environmental enteric dysfunction affect overgrowth restriction, infectious morbidity rate, and acquired lifelong risks among severe acute malnourished children. Also, despite acknowledging complexities of antimicrobial resistant enrichment, we explore and speculate over the links between virulence regulation and HGT as an indissociable part in the quest for new inflammatory niches by open genome bacteria, particularly when both collide in the most vulnerable.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43337091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-12DOI: 10.3389/frabi.2022.1003912
Kyle R. Leistikow, Rachelle E. Beattie, K. Hristova
The increasing global expansion of antimicrobial resistant infections warrants the development of effective antibiotic alternative therapies, particularly for use in livestock production, an agricultural sector that is perceived to disproportionately contribute to the antimicrobial resistance (AMR) crisis by consuming nearly two-thirds of the global antibiotic supply. Probiotics and probiotic derived compounds are promising alternative therapies, and their successful use in disease prevention, treatment, and animal performance commands attention. However, insufficient or outdated probiotic screening techniques may unintentionally contribute to this crisis, and few longitudinal studies have been conducted to determine what role probiotics play in AMR dissemination in animal hosts and the surrounding environment. In this review, we briefly summarize the current literature regarding the efficacy, feasibility, and limitations of probiotics, including an evaluation of their impact on the animal microbiome and resistome and their potential to influence AMR in the environment. Probiotic application for livestock is often touted as an ideal alternative therapy that might reduce the need for antibiotic use in agriculture and the negative downstream impacts. However, as detailed in this review, limited research has been conducted linking probiotic usage with reductions in AMR in agricultural or natural environments. Additionally, we discuss the methods, including limitations, of current probiotic screening techniques across the globe, highlighting approaches aimed at reducing antibiotic usage and ensuring safe and effective probiotic mediated health outcomes. Based on this information, we propose economic and logistical considerations for bringing probiotic therapies to market including regulatory roadblocks, future innovations, and the significant gaps in knowledge requiring additional research to ensure probiotics are suitable long-term options for livestock producers as an antibiotic alternative therapy.
{"title":"Probiotics beyond the farm: Benefits, costs, and considerations of using antibiotic alternatives in livestock","authors":"Kyle R. Leistikow, Rachelle E. Beattie, K. Hristova","doi":"10.3389/frabi.2022.1003912","DOIUrl":"https://doi.org/10.3389/frabi.2022.1003912","url":null,"abstract":"The increasing global expansion of antimicrobial resistant infections warrants the development of effective antibiotic alternative therapies, particularly for use in livestock production, an agricultural sector that is perceived to disproportionately contribute to the antimicrobial resistance (AMR) crisis by consuming nearly two-thirds of the global antibiotic supply. Probiotics and probiotic derived compounds are promising alternative therapies, and their successful use in disease prevention, treatment, and animal performance commands attention. However, insufficient or outdated probiotic screening techniques may unintentionally contribute to this crisis, and few longitudinal studies have been conducted to determine what role probiotics play in AMR dissemination in animal hosts and the surrounding environment. In this review, we briefly summarize the current literature regarding the efficacy, feasibility, and limitations of probiotics, including an evaluation of their impact on the animal microbiome and resistome and their potential to influence AMR in the environment. Probiotic application for livestock is often touted as an ideal alternative therapy that might reduce the need for antibiotic use in agriculture and the negative downstream impacts. However, as detailed in this review, limited research has been conducted linking probiotic usage with reductions in AMR in agricultural or natural environments. Additionally, we discuss the methods, including limitations, of current probiotic screening techniques across the globe, highlighting approaches aimed at reducing antibiotic usage and ensuring safe and effective probiotic mediated health outcomes. Based on this information, we propose economic and logistical considerations for bringing probiotic therapies to market including regulatory roadblocks, future innovations, and the significant gaps in knowledge requiring additional research to ensure probiotics are suitable long-term options for livestock producers as an antibiotic alternative therapy.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44485793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-16DOI: 10.3389/frabi.2022.957942
Nicholas M. Thomson, A. Turner, M. Yasir, Sarah Bastkowski, M. Lott, M. Webber, Ian G. Charles
We report here the identification of four gene functions of principal importance for the tolerance of meropenem stress in Escherichia coli: cell division, cell envelope synthesis and maintenance, ATP metabolism, and transcription regulation. The primary mechanism of β-lactam antibiotics such as meropenem is inhibition of penicillin binding proteins, thus interfering with peptidoglycan crosslinking, weakening the cell envelope, and promoting cell lysis. However, recent systems biology approaches have revealed numerous downstream effects that are triggered by cell envelope damage and involve diverse cell processes. Subpopulations of persister cells can also arise, which can survive elevated concentrations of meropenem despite the absence of a specific resistance factor. We used Transposon-Directed Insertion Sequencing with inducible gene expression to simultaneously assay the effects of upregulation, downregulation, and disruption of every gene in a model E. coli strain on survival of exposure to four concentrations of meropenem. Automated Gene Functional Classification and manual categorization highlighted the importance at all meropenem concentrations of genes involved in peptidoglycan remodeling during cell division, suggesting that cell division is the primary function affected by meropenem. Genes involved in cell envelope synthesis and maintenance, ATP metabolism, and transcriptional regulation were generally important at higher meropenem concentrations, suggesting that these three functions are therefore secondary or downstream targets. Our analysis revealed the importance of multiple two-component signal transduction mechanisms, suggesting an as-yet unexplored coordinated transcriptional response to meropenem stress. The inclusion of an inducible, transposon-encoded promoter allowed sensitive detection of genes involved in proton transport, ATP production and tRNA synthesis, for which modulation of expression affects survival in the presence of meropenem: a finding that would not be possible with other technologies. We were also able to suggest new targets for future antibiotic development or for synergistic effects between gene or protein inhibitors and existing antibiotics. Overall, in a single massively parallel assay we were able to recapitulate many of the findings from decades of research into β-lactam antibiotics, add to the list of genes known to be important for meropenem tolerance, and categorize the four principal gene functions involved.
{"title":"A whole-genome assay identifies four principal gene functions that confer tolerance of meropenem stress upon Escherichia coli","authors":"Nicholas M. Thomson, A. Turner, M. Yasir, Sarah Bastkowski, M. Lott, M. Webber, Ian G. Charles","doi":"10.3389/frabi.2022.957942","DOIUrl":"https://doi.org/10.3389/frabi.2022.957942","url":null,"abstract":"We report here the identification of four gene functions of principal importance for the tolerance of meropenem stress in Escherichia coli: cell division, cell envelope synthesis and maintenance, ATP metabolism, and transcription regulation. The primary mechanism of β-lactam antibiotics such as meropenem is inhibition of penicillin binding proteins, thus interfering with peptidoglycan crosslinking, weakening the cell envelope, and promoting cell lysis. However, recent systems biology approaches have revealed numerous downstream effects that are triggered by cell envelope damage and involve diverse cell processes. Subpopulations of persister cells can also arise, which can survive elevated concentrations of meropenem despite the absence of a specific resistance factor. We used Transposon-Directed Insertion Sequencing with inducible gene expression to simultaneously assay the effects of upregulation, downregulation, and disruption of every gene in a model E. coli strain on survival of exposure to four concentrations of meropenem. Automated Gene Functional Classification and manual categorization highlighted the importance at all meropenem concentrations of genes involved in peptidoglycan remodeling during cell division, suggesting that cell division is the primary function affected by meropenem. Genes involved in cell envelope synthesis and maintenance, ATP metabolism, and transcriptional regulation were generally important at higher meropenem concentrations, suggesting that these three functions are therefore secondary or downstream targets. Our analysis revealed the importance of multiple two-component signal transduction mechanisms, suggesting an as-yet unexplored coordinated transcriptional response to meropenem stress. The inclusion of an inducible, transposon-encoded promoter allowed sensitive detection of genes involved in proton transport, ATP production and tRNA synthesis, for which modulation of expression affects survival in the presence of meropenem: a finding that would not be possible with other technologies. We were also able to suggest new targets for future antibiotic development or for synergistic effects between gene or protein inhibitors and existing antibiotics. Overall, in a single massively parallel assay we were able to recapitulate many of the findings from decades of research into β-lactam antibiotics, add to the list of genes known to be important for meropenem tolerance, and categorize the four principal gene functions involved.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46048747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-09DOI: 10.3389/frabi.2022.928365
R. Hammond, Frank Kloprogge, O. Pasqua, S. Gillespie
Background Tuberculosis treatment duration is long and does not guarantee eradication of infection. Shorter treatment regimens are a critical research objective to improve uptake and reduce the risk of relapse and bacterial resistance. The explanation for the need to continue treatment after patients are culture negative remains elusive. We have previously shown that the presence of lipid inclusions in mycobacterial cells is associated with an increase in antibiotic resistance. Aim We investigate the bactericidal effect of isoniazid and rifampicin on the expression of lipid inclusions and characterize the degree of the associated phenotypic antibiotic resistance to a range of anti-tuberculosis agents in current use. Methods Antibiotic killing effect for both M. tuberculosis and M. komossense were investigated by both hollow fiber bioreactor (HFS) studies and static time kill curve (STKC) experiments. Following STKC cultures were stained with resazurin, Sytox green and Nile red to establish their live/dead (resazurin positive/Sytox positive) and lipid inclusion status, respectively. In addition, M. komossense was studied in the hollow fiber bioreactor model (HFS) and exposed to isoniazid (H) and rifampicin (R). The MIC of current antituberculosis agents for cells from the treated hollow fiber experiments were tested. Results Antibiotic killing was similar for both species. For M. komossense; isoniazid was ineffective at the established MIC (1 mg/L) in the hollow fiber bioreactor but rifampicin reduced the viable count rapidly at MIC (0.4 mg/L). When the two drugs were combined at their respective MICs the killing effect was significant and greater than separately. Cells exposed to isoniazid (1x and 9x MIC) for 168 h showed considerable numbers of recoverable viable cells when compared with a combination of 1x MIC R & H where there were no viable cells detectable. For both drugs the number of lipid body positive cells increased over time and this effect was most pronounced for isoniazid and was associated with phenotypic resistance to multiple anti-tuberculosis drugs. Conclusion Our results showed that isoniazid is a potent stimulator of lipid body accumulation, culture persistence, and phenotypic resistance to multiple anti-tuberculosis drugs. These findings emphasize the importance of understanding mechanisms of drug-drug interactions and phenotypic resistance in regimen building.
{"title":"Implications of drug-induced phenotypical resistance: Is isoniazid radicalizing M. tuberculosis?","authors":"R. Hammond, Frank Kloprogge, O. Pasqua, S. Gillespie","doi":"10.3389/frabi.2022.928365","DOIUrl":"https://doi.org/10.3389/frabi.2022.928365","url":null,"abstract":"Background Tuberculosis treatment duration is long and does not guarantee eradication of infection. Shorter treatment regimens are a critical research objective to improve uptake and reduce the risk of relapse and bacterial resistance. The explanation for the need to continue treatment after patients are culture negative remains elusive. We have previously shown that the presence of lipid inclusions in mycobacterial cells is associated with an increase in antibiotic resistance. Aim We investigate the bactericidal effect of isoniazid and rifampicin on the expression of lipid inclusions and characterize the degree of the associated phenotypic antibiotic resistance to a range of anti-tuberculosis agents in current use. Methods Antibiotic killing effect for both M. tuberculosis and M. komossense were investigated by both hollow fiber bioreactor (HFS) studies and static time kill curve (STKC) experiments. Following STKC cultures were stained with resazurin, Sytox green and Nile red to establish their live/dead (resazurin positive/Sytox positive) and lipid inclusion status, respectively. In addition, M. komossense was studied in the hollow fiber bioreactor model (HFS) and exposed to isoniazid (H) and rifampicin (R). The MIC of current antituberculosis agents for cells from the treated hollow fiber experiments were tested. Results Antibiotic killing was similar for both species. For M. komossense; isoniazid was ineffective at the established MIC (1 mg/L) in the hollow fiber bioreactor but rifampicin reduced the viable count rapidly at MIC (0.4 mg/L). When the two drugs were combined at their respective MICs the killing effect was significant and greater than separately. Cells exposed to isoniazid (1x and 9x MIC) for 168 h showed considerable numbers of recoverable viable cells when compared with a combination of 1x MIC R & H where there were no viable cells detectable. For both drugs the number of lipid body positive cells increased over time and this effect was most pronounced for isoniazid and was associated with phenotypic resistance to multiple anti-tuberculosis drugs. Conclusion Our results showed that isoniazid is a potent stimulator of lipid body accumulation, culture persistence, and phenotypic resistance to multiple anti-tuberculosis drugs. These findings emphasize the importance of understanding mechanisms of drug-drug interactions and phenotypic resistance in regimen building.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47849827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-07DOI: 10.3389/frabi.2022.980686
M. Alsamawi, Anwar I. Joudeh, Yaseer Eldeeb, Ayman Al-Dahshan, F. Khan, W. Ghadban, M. Almaslamani, A. Alkhal
Background The incidence of ESBL infections is exponentially increasing with variable prevalence among geographical areas and treatment settings. Identifying local prevalence rate and patient-related factors will help in earlier recognition and initiation of appropriate antibiotics treatment of patients with ESBL infections. Methods Retrospective analysis of all positive cultures for ESBL producing Enterobacteriaceae collected in Al-Khor hospital from January 2010 to December 2012. ESBL bacterial isolates reported as cephalosporin-resistant or ESBL using the automated VITEK Gram-Negative Susceptibility System with cards GNS 206 and 121 were screened for ESBL detection using the disk diffusion method in keeping with the Clinical and Laboratory Standards Institute. Both descriptive and analytic statistics were applied when appropriate, and univariate analysis was used to identify significant factors. Results Most of the ESBL-producing bacterial isolates were E. coli, which were also resistant to other classes of antimicrobials. Meropenem, amikacin and nitrofurantoin retained good coverage to most isolates. Klebsiella pneumonia infection was most likely associated with diabetes mellitus (p = 0.004), hospital-acquired infection (p = 0.046) and with more severe infection (p = 0.006). ESBL associated hospital-acquired infections were more likely to occur in older patients, those with comorbidities and with invasive device use. ESBL-associated urinary tract infections were most commonly community-acquired while ESBL associated respiratory tract infections were acquired from hospitals (p = < 0.001). Factors associated with mortality include treatment in the ICU (OR 104.8 [9.82–1116.96] p < 0.001), sepsis/septic shock (OR 20.80 (5.68–76.12) p < 0.001), hospital-acquired infections (OR 8.80 [1.88–41.16] p = 0.006) and bacteremia (OR 8.80 [1.63–47.5] p = 0.013). Conclusion Multiple risk factors were associated with ESBL infections both in the community and hospital setting. Prediction tools are needed to improve the protocol of appropriate empiric antibiotic selection while preserving antimicrobial stewardship recommendations.
{"title":"Epidemiology of extended-spectrum beta-lactamase producing Enterobacteriaceae in Qatar: A 3-year hospital-based study","authors":"M. Alsamawi, Anwar I. Joudeh, Yaseer Eldeeb, Ayman Al-Dahshan, F. Khan, W. Ghadban, M. Almaslamani, A. Alkhal","doi":"10.3389/frabi.2022.980686","DOIUrl":"https://doi.org/10.3389/frabi.2022.980686","url":null,"abstract":"Background The incidence of ESBL infections is exponentially increasing with variable prevalence among geographical areas and treatment settings. Identifying local prevalence rate and patient-related factors will help in earlier recognition and initiation of appropriate antibiotics treatment of patients with ESBL infections. Methods Retrospective analysis of all positive cultures for ESBL producing Enterobacteriaceae collected in Al-Khor hospital from January 2010 to December 2012. ESBL bacterial isolates reported as cephalosporin-resistant or ESBL using the automated VITEK Gram-Negative Susceptibility System with cards GNS 206 and 121 were screened for ESBL detection using the disk diffusion method in keeping with the Clinical and Laboratory Standards Institute. Both descriptive and analytic statistics were applied when appropriate, and univariate analysis was used to identify significant factors. Results Most of the ESBL-producing bacterial isolates were E. coli, which were also resistant to other classes of antimicrobials. Meropenem, amikacin and nitrofurantoin retained good coverage to most isolates. Klebsiella pneumonia infection was most likely associated with diabetes mellitus (p = 0.004), hospital-acquired infection (p = 0.046) and with more severe infection (p = 0.006). ESBL associated hospital-acquired infections were more likely to occur in older patients, those with comorbidities and with invasive device use. ESBL-associated urinary tract infections were most commonly community-acquired while ESBL associated respiratory tract infections were acquired from hospitals (p = < 0.001). Factors associated with mortality include treatment in the ICU (OR 104.8 [9.82–1116.96] p < 0.001), sepsis/septic shock (OR 20.80 (5.68–76.12) p < 0.001), hospital-acquired infections (OR 8.80 [1.88–41.16] p = 0.006) and bacteremia (OR 8.80 [1.63–47.5] p = 0.013). Conclusion Multiple risk factors were associated with ESBL infections both in the community and hospital setting. Prediction tools are needed to improve the protocol of appropriate empiric antibiotic selection while preserving antimicrobial stewardship recommendations.","PeriodicalId":73065,"journal":{"name":"Frontiers in antibiotics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43931137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}