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Analysis of the Virulence of a Lethal, Carbapenem-resistant Hypervirulent Klebsiella pneumoniae ST-11 Producing KPC-33. 分析产生 KPC-33 的致命、耐碳青霉烯类抗生素的高病毒性肺炎克雷伯氏菌 ST-11 的毒性。
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-23 DOI: 10.1016/j.micpath.2024.107154
Yuzhong Yan, Nana Kong, Yuxiao Niu, Kangde Sun, Wenxia Zhang
<p><strong>Objective: </strong>Hypervirulent and carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) poses a serious threat to public health. Here, we analyse a case of systemic infection caused by a hv-CRKP, which ultimately led to the patient's death from sepsis. And a total of 30 CRKP were analyzed to elucidate the molecular epidemiological features of CRKP in the hospital, and to provide a basis for clinical anti-infective therapy.</p><p><strong>Methods: </strong>In this case, a total of 7 K. pneumoniae strains were isolated from the blood, sputum, urine, and feces of the patient. The Vitek-2 compact system was used to identify the strains and perform antimicrobial susceptibility testing. Biofilm formation, siderophore production assays and Galleria mellonella infection model were used to verify the virulence phenotypes of the strains in the case. Whole-genome sequencing was conducted on the four hv-CRKP isolated from different samples in the case and 26 other CRKP collected in our hospital from September to November in 2022, using the Illumina Hiseq 6000 high-throughput sequencing platform to analyse the resistance and virulence genes.</p><p><strong>Results: </strong>In the case, after 7 days of treatment with ceftazidime-avibactam (CZA), the resistance profile of the strains changed. The strain that was initially sensitive to CZA developed to resistant, resistant to imipenem (IPM) developed to sensitive, and resistant to meropenem (MEM) developed to intermediate. Whole-genome sequencing revealed that the four strains in the case were all ST11-KL64 K. pneumoniae, and the change in resistance phenotype was due to the mutation from bla<sub>KPC-2</sub> to bla<sub>KPC-33</sub>. KPN7 had a total of six plasmids, with siderophore-related genes iucABCD and iutA, and mucoid phenotype-related gene rmpA2 located on plasmid p4-KPN7; resistance genes bla<sub>KPC-33</sub>, bla<sub>TEM-1B</sub>, and bla<sub>CTX-M-65</sub> located on plasmid p5-KPN7; and virulence genes fim, irp, iutA, and ybt located on the chromosome. Biofilm formation and siderophore production assays confirmed that the seven K. pneumoniae strains isolated in this case had strong biofilm formation and siderophore production capabilities. Galleria mellonella Infection Model showed that KPN4 and KPN7 was phenotypically highly virulent and KPN7 performed lower virulence compared to KPN4. Apart from the 4 hv-CRKP strains, other 26 CRKP strains all carried bla<sub>KPC-2</sub>, and 69.2% (18/26) were ST-11 and 30.8%(8/26) were ST-15. And 83.3% (15/18) were ST11-KL64 strains, followed by ST11-KL25 strains 11.1%(2/18) and ST11-KL47 strain 5.6%(1/18). All the eight ST-15 strains were KL-19.</p><p><strong>Conclusion: </strong>The ST11-KL64 hv-CRKP clone spread widely in ICU carried numerous resistance and virulence genes, and under antibiotic pressure, they easily underwent mutations resulting in changes in resistance phenotypes, especially in mutations of bla<sub>KPC-2</sub> gene in acquiring r
目的:高病毒性和耐碳青霉烯类肺炎克雷伯氏菌(hv-CRKP)对公共卫生构成严重威胁。在此,我们分析了一例由 hv-CRKP 引起的全身感染病例,该病例最终导致患者死于败血症。并对30例CRKP进行了分析,以阐明医院中CRKP的分子流行病学特征,为临床抗感染治疗提供依据:本病例中,从患者的血液、痰液、尿液和粪便中共分离出 7 株肺炎克雷伯菌。使用 Vitek-2 紧凑型系统对菌株进行鉴定,并进行抗菌药敏感性测试。生物膜形成、嗜苷酸生成试验和Galleria mellonella感染模型被用来验证病例中菌株的毒力表型。利用Illumina Hiseq 6000高通量测序平台,对病例中从不同样本中分离出的4株hv-CRKP和2022年9月至11月期间在本院收集的其他26株CRKP进行了全基因组测序,以分析抗性基因和毒力基因:结果发现,在使用头孢他啶-阿维巴坦(CZA)治疗7天后,菌株的耐药性发生了变化。最初对头孢他啶-阿维菌素(CZA)敏感的菌株发展为耐药菌株,对亚胺培南(IPM)耐药的菌株发展为敏感菌株,对美罗培南(MEM)耐药的菌株发展为中间耐药菌株。全基因组测序显示,该病例中的四株菌株均为 ST11-KL64 K. pneumoniae,耐药表型的改变是由于 blaKPC-2 突变为 blaKPC-33 所致。KPN7 共有 6 个质粒,其中嗜苷酸相关基因 iucABCD 和 iutA 以及黏液表型相关基因 rmpA2 位于质粒 p4-KPN7;抗性基因 blaKPC-33、blaTEM-1B 和 blaCTX-M-65 位于质粒 p5-KPN7;毒力基因 fim、irp、iutA 和 ybt 位于染色体上。生物膜形成和嗜酸性物质产生试验证实,在本病例中分离出的 7 株肺炎克氏菌具有很强的生物膜形成和嗜酸性物质产生能力。Galleria mellonella 感染模型显示,KPN4 和 KPN7 的表型毒力很强,而 KPN7 的毒力低于 KPN4。除4株hv-CRKP外,其他26株CRKP均携带blaKPC-2,69.2%(18/26)为ST-11,30.8%(8/26)为ST-15。83.3%(15/18)是 ST11-KL64 菌株,其次是 ST11-KL25 菌株 11.1%(2/18)和 ST11-KL47 菌株 5.6%(1/18)。所有 8 株 ST-15 菌株均为 KL-19.Conclusion 菌株:结论:在ICU广泛传播的ST11-KL64 hv-CRKP克隆携带大量耐药和毒力基因,在抗生素压力下容易发生突变,导致耐药表型发生变化,尤其是blaKPC-2基因突变后获得对CZA的耐药性。因此,临床上应关注此类菌株,并根据菌株对抗菌药物的敏感性及时调整抗生素的使用。
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引用次数: 0
Biofilm Battleground: Unveiling the hidden challenges, current approaches and future perspectives in combating biofilm associated bacterial infections. 生物膜战场:揭示对抗生物膜相关细菌感染的隐性挑战、当前方法和未来前景。
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-23 DOI: 10.1016/j.micpath.2024.107155
Sandeep Patra, Sumana Saha, Randhir Singh, Nandini Tomar, Pallavi Gulati

A biofilm is a complex aggregation of microorganisms, either of the same or different species, that adhere to a surface and are encased in an extracellular polymeric substances (EPS) matrix. Quorum sensing (QS) and biofilm formation are closely linked, as QS genes regulate the development, maturation, and breakdown of biofilms. Inhibiting QS can be utilized as an effective approach to combat the impacts of biofilm infection. The impact of biofilms includes chronic infections, industrial biofouling, infrastructure corrosion, and environmental contamination as well. Therefore, a deep understanding of biofilms is crucial for enhancing public health, advancing industrial processes, safeguarding the environment, and deepening our knowledge of microbial life as well. This review aims to offer a comprehensive examination of challenges posed by bacterial biofilms, contemporary approaches and strategies for effectively eliminating biofilms, including the inhibition of quorum sensing pathways, while also focusing on emerging technologies and techniques for biofilm treatment. In addition, future research is projected to target the challenges associated with the bacterial biofilms, striving to develop new approaches and improve existing strategies for their effective control and eradication.

生物膜是同种或不同种微生物的复杂聚集体,它们附着在表面并被细胞外聚合物物质(EPS)基质包裹。法定量感应(QS)与生物膜的形成密切相关,因为 QS 基因调控生物膜的发育、成熟和分解。抑制 QS 可以作为对抗生物膜感染影响的有效方法。生物膜的影响包括慢性感染、工业生物污染、基础设施腐蚀以及环境污染。因此,深入了解生物膜对于提高公众健康水平、促进工业流程、保护环境以及加深我们对微生物生命的了解至关重要。本综述旨在全面探讨细菌生物膜带来的挑战、有效消除生物膜的当代方法和策略(包括抑制法定量感应途径),同时关注生物膜处理的新兴技术和工艺。此外,预计未来的研究将针对与细菌生物膜相关的挑战,努力开发新方法并改进现有策略,以有效控制和消除生物膜。
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引用次数: 0
Toxicological Evaluation of Salmonella Phage NINP13076 in BALB/c Mice: Histopathological Studies. 沙门氏菌噬菌体 NINP13076 在 BALB/c 小鼠中的毒理学评估:组织病理学研究。
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-23 DOI: 10.1016/j.micpath.2024.107146
R Naveen Kumar, M V Surekha, S D G Gowthami, A K Aditi, M Satyavani, K Satyanarayana, R Hemalatha, P Uday Kumar

Salmonella spp. represent a significant etiological agent of foodborne illnesses and constitute a notable public health challenge on a global scale. Effectively managing Salmonella contamination within the food supply chain is imperative, as it represents a significant threat to public health, potentially leading to severe illnesses with fatal consequences. A novel bio-preservative agent is required to combat Salmonella food contamination during different stages of the food supply chain. Bacteriophages are acknowledged for their safety and recognized for their efficacy in bio-food preservation. Given their consumption together alongside food, it becomes pivotal to assess their potential toxicity concerning the probiotic gut microbiota. In this research, BALB/c mice were employed to evaluate the sub-chronic oral toxicity of bacteriophages targeting Salmonella. Following 28 consecutive days of sub-chronic administration of the Salmonella phage through oral means, histopathological examinations of vital organs, including the lung, kidneys, heart, liver, and intestine, revealed normal organ structures and no significant pathological abnormalities, in both the control and experimental groups. No physical or behavioural change was noticed in the experimental mice. Furthermore, the proliferation of indicative probiotic bacteria persisted unchanged even following a 24-hour incubation with the Salmonella phage. The body weight of both the control and experimental subjects, along with a comparative analysis of urine test results, exhibited no variations. Notably, the phages demonstrated no discernible impact on the probiotic microbiota, specifically the Lactobacillus and Bifidobacterium species isolated from the caecum of both mice that received treatment and those that did not. In untreated animals, the probiotic population (mean log CFU/ml) ranged from 1.9 to 2.4 log and 2.4 to 2.5 log, while in treated mice, it ranged from 2.0 to 2.3 log and 2.3 to 2.4 log for the Lactobacillus and Bifidobacterium species, respectively. The results of the investigation indicate that the oral administration of the lytic Salmonella phage showed no observable adverse effects on the animals, indicating an absence of harm.

沙门氏菌是食源性疾病的重要病原菌,在全球范围内构成了一个显著的公共卫生挑战。有效控制食品供应链中的沙门氏菌污染势在必行,因为它对公众健康构成了重大威胁,有可能导致严重疾病,造成致命后果。需要一种新型生物防腐剂来应对食品供应链不同阶段的沙门氏菌食品污染。噬菌体在生物食品保鲜方面的安全性和功效已得到公认。鉴于噬菌体与食物一起食用,评估其对益生菌肠道微生物群的潜在毒性变得至关重要。本研究采用 BALB/c 小鼠来评估针对沙门氏菌的噬菌体的亚慢性口服毒性。通过口服沙门氏菌噬菌体连续亚慢性给药 28 天后,重要器官(包括肺、肾、心脏、肝脏和肠道)的组织病理学检查显示,对照组和实验组的器官结构正常,无明显病理异常。实验组小鼠的身体和行为没有发生变化。此外,即使在与沙门氏菌噬菌体培养 24 小时后,指示性益生菌的增殖仍保持不变。对照组和实验组的体重以及尿液检测结果的比较分析均未显示出任何变化。值得注意的是,噬菌体对益生菌微生物群没有明显影响,特别是从接受治疗和未接受治疗的小鼠盲肠中分离出的乳杆菌和双歧杆菌。在未接受治疗的小鼠中,益生菌数量(平均对数 CFU/毫升)分别为 1.9 至 2.4 log 和 2.4 至 2.5 log,而在接受治疗的小鼠中,乳酸杆菌和双歧杆菌数量分别为 2.0 至 2.3 log 和 2.3 至 2.4 log。调查结果表明,口服溶解性沙门氏菌噬菌体对动物没有明显的不良影响,表明没有危害。
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引用次数: 0
Novel natural and economic approach for controlling methicillin-resistant Staphylococcus aureus using apple cider vinegar 利用苹果醋控制耐甲氧西林金黄色葡萄球菌的新型天然经济方法
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-23 DOI: 10.1016/j.micpath.2024.107150
Sherief M. Abdel-Raheem , Eman M. Abouelhassan , Mostafa Mandour , Waleed Rizk El-Ghareeb , Mohamed Shawky , Reham M. Eltarabili
Methicillin-resistant Staphylococcus aureus (MRSA) constitutes a significant health concern because it promotes infectious mastitis in dairy animals and poses a hazard risk to humans. Controlling MRSA infections is a growing challenge on a global scale because of the bacteria's toxicity and its capacity to develop multidrug resistance (MDR). Combating against MDR bacteria and the spread of infectious diseases needs natural antibacterial alternatives to minimize the economic losses of mastitis. The average treatment cost in Egypt was highlighted. The antibacterial effect of apple cider vinegar (ACV) against MDR-MRSA isolates was evaluated, also the study aimed at profiling antimicrobial resistance genes in MRSA isolates. The incidence of mastitis in cows was more than in buffaloes, and the average total treatment cost was estimated at 82 million EGP from 2016 to 2021 (around 14 million EGP annually). Of the 22 S. aureus isolates (20 %), of which (59.1 % were from cows and 40.9 % from buffaloes), 19 (86.4 %) were confirmed as MRSA. All MRSA isolates exhibited resistance to clindamycin (94.7 %), then both ampicillin and doxycycline (84.2 %), and ampicillin and sulbactam, erythromycin and Fosfomycin (each, 78.9 %). Vancomycin, ciprofloxacin, and levofloxacin can be used to treat MRSA. The prevalence of MDR was significantly high, with 94.7 % of the cases having multiple antimicrobial resistance (MAR) indices ranging from 0.25 to 0.75. All MRSA isolates tested positive for mecA, 89.5 % for the blaZ gene, 84.2 % for tetM, and 73.4 % for ermB. In vitro, the antibacterial properties of ACV were demonstrated to be superior by our results which demonstrate a zone of inhibition with diameters ranging from 20 to 40 mm detected by Agar well diffusion technique and MIC's (Minimal Inhibitory Concentration) ranging from 2 to 4 μg/ml. Some isolates possess MBC (Minimal Bactericidal Concentration) values at the same MIC. This research proposes the potential of ACV to act as a promising antibacterial alternative against MRSA. This can help minimize the health problem of antibiotic-resistant bacteria and improve the efficiency of dairy farms. Further studies are recommended to determine the proper dosage for field administration.
耐甲氧西林金黄色葡萄球菌(MRSA)会引发乳牛传染性乳腺炎,并对人类造成危害,因此是一个重大的健康问题。由于 MRSA 细菌的毒性及其产生多重耐药性(MDR)的能力,控制 MRSA 感染在全球范围内成为一项日益严峻的挑战。对抗 MDR 细菌和传染病的传播需要天然的抗菌替代品,以尽量减少乳腺炎造成的经济损失。重点介绍了埃及的平均治疗费用。该研究评估了苹果醋 (ACV) 对 MDR-MRSA 分离物的抗菌效果,同时还旨在分析 MRSA 分离物中的抗菌药耐药性基因。奶牛乳腺炎的发病率高于水牛,从 2016 年到 2021 年,平均总治疗费用估计为 8200 万埃及镑(每年约 1400 万埃及镑)。在 22 个金黄色葡萄球菌分离物(20%)中(59.1% 来自奶牛,40.9% 来自水牛),19 个(86.4%)被证实为 MRSA。所有 MRSA 分离物均对克林霉素(94.7%)、氨苄西林和强力霉素(84.2%)、氨苄西林和舒巴坦、红霉素和磷霉素(各占 78.9%)产生抗药性。万古霉素、环丙沙星和左氧氟沙星可用于治疗 MRSA。多重耐药性的发生率很高,94.7%的病例具有多重抗菌药耐药性(MAR),耐药性指数从0.25到0.75不等。所有 MRSA 分离物的 mecA、blaZ、tetM 和 ermB 检测结果均呈阳性,分别占 89.5%、84.2% 和 73.4%。体外实验结果表明,ACV 的抗菌性能优越,琼脂井扩散技术检测到的抑菌区直径为 20 至 40 毫米,MIC(最小抑菌浓度)为 2 至 4 微克/毫升。一些分离物的 MBC(最低杀菌浓度)值与 MIC 值相同。这项研究表明,ACV 有潜力成为抗 MRSA 的一种有前途的抗菌替代品。这有助于最大限度地减少抗生素耐药菌对健康造成的影响,并提高奶牛场的效率。建议开展进一步研究,以确定现场用药的适当剂量。
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引用次数: 0
Azithromycin inhibits the intracellular persistence of Acinetobacter baumannii by inducing host cell autophagy in human bronchial epithelial cells. 阿奇霉素通过诱导宿主细胞自噬抑制鲍曼不动杆菌在人支气管上皮细胞内的持续存在。
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-23 DOI: 10.1016/j.micpath.2024.107152
Bangbi Weng, Yuliang Li, Wei Feng, Pu Yao, Yu Wang, Qianmei Wang, Xiaowen Wang, Yang Li, Li Li, Qian Wang

The invasion of host cells by bacteria, leading to intracellular infections, is a major cause of infection recurrence. Drug-resistant Acinetobacter baumannii (A. baumannii) is one of the most challenging public health issues worldwide, with very limited clinical treatment options available. A. baumannii has been found to be able to invade host cells and proliferate within them in recent studies. In addition to the direct antimicrobial effect of antibiotics, the activation of host autophagic flux also plays an important role in eliminating intracellular pathogens. Herein, this study aimes to evaluate the clearance effect of antibiotics on intracellular A. baumannii both in vivo and in vitro, and explore the relationship between this effect and autophagy. The results showed that intracellular pathogens resulted in a significant increase in the minimum bactericidal concentration, while azithromycin can significantly eliminate intracellular A. baumannii in vitro and in vivo. Notably, 60 μg/mL azithromycin demonstrated intracellular clearance against multidrug-resistant A. baumannii and markedly induced autophagosomes in BEAS-2B cells with a mild stimulation of autophagosomes degradation. These findings indicated that azithromycin can significantly clear intracellular A. baumannii and its ability to clear intracellular A. baumannii may be related to the stimulation of autophagosome formation and the induction of host autophagy, which has important implications for the clinical treatment of A. baumannii infections, especially when intracellular infections are present.

细菌入侵宿主细胞导致细胞内感染是感染复发的主要原因。耐药鲍曼不动杆菌(A. baumannii)是全球最具挑战性的公共卫生问题之一,临床治疗方案非常有限。最近的研究发现,鲍曼不动杆菌能够侵入宿主细胞并在其中增殖。除了抗生素的直接抗菌作用外,宿主自噬通量的激活在消灭细胞内病原体方面也发挥着重要作用。本研究旨在评估抗生素在体内和体外对细胞内鲍曼不动杆菌的清除作用,并探讨这种作用与自噬之间的关系。结果表明,细胞内病原体导致最低杀菌浓度显著增加,而阿奇霉素能在体外和体内显著清除细胞内鲍曼不动杆菌。值得注意的是,60 μg/mL的阿奇霉素对耐多药鲍曼尼氏菌有细胞内清除作用,并能明显诱导BEAS-2B细胞中的自噬体,轻度刺激自噬体降解。这些研究结果表明,阿奇霉素能显著清除胞内鲍曼尼菌,其清除胞内鲍曼尼菌的能力可能与刺激自噬体形成和诱导宿主自噬有关,这对临床治疗鲍曼尼菌感染,尤其是存在胞内感染时具有重要意义。
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引用次数: 0
The RNA Chaperone Protein ProQ is a pleiotropic regulator in enteropathogenic Escherichia coli. RNA 伴侣蛋白 ProQ 是肠致病性大肠杆菌的一种多效调节因子。
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-23 DOI: 10.1016/j.micpath.2024.107153
Alexa Mihaita, Abigail Robinson, Emily Costello, Mary Marino, Zoe Mrozek, Lianna Long, Aidan Fogarty, Marisa Egan, Shantanu Bhatt

Enteropathogenic Escherichia coli (EPEC) is a gastrointestinal pathogen that affects individuals of all age groups, with infections ranging from subclinical colonization to acute or persistent diarrhea. The bacterium's ability to cause diarrhea depends on the locus of enterocyte effacement (LEE) pathogenicity island. Although regulation of the LEE has been systematically characterized, until the last decade, these studies were limited to transcriptional control. Posttranscriptional regulation of the LEE is an underappreciated and understudied area of gene regulation. In the past few years, multiple reports have shed light on the roles of RNA-binding proteins, such as Hfq and CsrA, that modulate virulence in EPEC. This study was undertaken to explore the role of another RNA chaperone protein, ProQ, in the pathophysiology of EPEC. Our results suggest that deletion of proQ globally derepresses gene expression from the LEE in lysogeny broth (LB) suggesting that ProQ is a negative regulator of the LEE. Further interrogation of the role of ProQ in regulating the LEE-encoded type III secretion system revealed that ProQ globally silences the LEE by downregulating the expression of PerC - a prominent transcriptional activator of the LEE master regulator ler, which, in turn leads to the observed repression from the other LEE operons. Furthermore, ProQ appears to moonlight as it affects other physiological processes including type IV pili biogenesis, flagellar-motility, biofilm formation, tryptophan metabolism, and antibiotic resistance. Our study provides the very first evidence to implicate ProQ as a pleiotropic regulator in EPEC.

肠致病性大肠杆菌(EPEC)是一种胃肠道病原体,可影响所有年龄组的人,感染范围从亚临床定植到急性或持续性腹泻。该细菌导致腹泻的能力取决于肠细胞脱落位点(LEE)致病性岛。尽管人们已经系统地描述了对LEE的调控,但直到最近十年,这些研究都仅限于转录调控。LEE的转录后调控是基因调控中一个未被重视和研究的领域。在过去几年中,多篇报道揭示了 RNA 结合蛋白(如 Hfq 和 CsrA)在 EPEC 毒力调节中的作用。本研究旨在探讨另一种 RNA 伴侣蛋白 ProQ 在 EPEC 病理生理学中的作用。我们的结果表明,在溶菌肉汤(LB)中,缺失 ProQ 会全面抑制 LEE 的基因表达,这表明 ProQ 是 LEE 的负调控因子。对 ProQ 在调控由 LEE 编码的 III 型分泌系统中的作用的进一步研究表明,ProQ 通过下调 PerC(LEE 主调控因子 ler 的一个重要转录激活因子)的表达全面抑制了 LEE,这反过来又导致了所观察到的其他 LEE 操作子的抑制。此外,ProQ似乎还能影响其他生理过程,包括IV型纤毛生物生成、鞭毛运动、生物膜形成、色氨酸代谢和抗生素耐药性。我们的研究首次提供了证据,证明 ProQ 是 EPEC 的多效调节因子。
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引用次数: 0
Bacterial infections associated with cutaneous leishmaniasis in Salah Al-Din province, Iraq 伊拉克萨拉赫丁省与皮肤利什曼病相关的细菌感染。
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-22 DOI: 10.1016/j.micpath.2024.107144
Noor Waleed Al-Alousy, Fatima Shihab Al-Nasiri
Bacterial co-infection with cutaneous leishmaniasis (CL) can effect on the clinical appearance of lesions and delay the healing process. The pattern of bacterial pathogens involved has rarely been investigated in Iraq. The aim of present study was to identify the bacterial agents contaminating CL and their susceptibility to commonly used antibiotics.
Four hundred cases of CL were diagnosed in Salah El-Din General Hospital, Iraq. A total of 424 ulcer samples obtained from 400 patients of CL were cultured, and all isolates were diagnosed based on phenotypic characteristics of colonies, bacterial cells and using biochemical tests.
No bacterial growth appeared in 124 cases (29.25 %) of the total number of examined ulcer samples, whereas 300 cases (70.75 %) were contaminated. Both Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes) and Gram-negative bacterial species (Escherichi coli, Klebsiella spp., Pseudomonas aeruginosa) were present. The infection with S. aureus represented the highest percentage (26.42 %), while Ps. aeruginosa had the lowest percentage (2.83 %) compared with other bacterial infections. The sensitivity of the isolated bacteria associated with CL was tested against a number of antibiotics (Amoxicillin, Ampicillin, Cefixime, Chloramphenlcol, Doxycycline, Tetracycline). Resistance to Amoxicillin, Ampicillin, and Cefixime was generally high. While, Chloramphenicol showed absolute effectiveness against isolated bacteria.
The results of the current study show that bacterial infections should be considered in diagnosing and treating CL lesions, with Chloramphenicol demonstrating the highest efficiency in treating such bacterial infections. The present study also suggests that hygiene, use of suitable disinfectants, controlling of antibiotic administration and prescription in hospitals and pharmacies must be ensured. In addition, regular surveillance in the endemic area will help control bacterial co-infection and hamper the occurrence of drug-resistant pathogens. The lesion care and management of secondary bacterial infection are essential and anti -leishmanial therapy in CL may be more effective when combined with antibiotics.
Future molecular studies are needed to identify the species of Leishmania causing CL in Iraq to gain a better understanding of their clinical manifestations (dry or moist ulcers) and their associated bacteria.
皮肤利什曼病(CL)的细菌合并感染会影响皮损的临床表现并延迟愈合过程。在伊拉克,有关细菌病原体模式的调查很少。本研究旨在确定污染皮肤利什曼病的细菌病原体及其对常用抗生素的敏感性。伊拉克萨拉赫丁综合医院共诊断出 400 例 CL 病例。对从 400 名 CL 患者身上获得的 424 份溃疡样本进行了培养,并根据菌落、细菌细胞的表型特征和生化测试对所有分离菌进行了诊断。在所有检查过的溃疡样本中,有 124 例(29.25%)没有细菌生长,而有 300 例(70.75%)受到污染。革兰氏阳性菌(金黄色葡萄球菌、表皮葡萄球菌、化脓性链球菌)和革兰氏阴性菌(大肠埃希氏菌、克雷伯氏菌属、铜绿假单胞菌)都存在。与其他细菌感染相比,金黄色葡萄球菌感染的比例最高(26.42%),而铜绿假单胞菌感染的比例最低(2.83%)。与 CL 相关的分离细菌对多种抗生素(阿莫西林、氨苄西林、头孢克肟、氯霉素、强力霉素、四环素)进行了敏感性测试。对阿莫西林、氨苄西林和头孢克肟的耐药性普遍较高。而氯霉素对分离出的细菌绝对有效。本研究结果表明,在诊断和治疗 CL 病变时应考虑细菌感染,其中氯霉素治疗此类细菌感染的效率最高。本研究还建议,必须确保医院和药房的卫生、使用合适的消毒剂、控制抗生素的使用和处方。此外,在流行地区进行定期监测将有助于控制细菌合并感染,并阻止耐药病原体的出现。病变护理和继发细菌感染的处理至关重要,CL 的抗利什曼病疗法与抗生素联合使用可能会更有效。未来需要进行分子研究,以确定在伊拉克引起 CL 的利什曼病菌种类,从而更好地了解其临床表现(干性或湿性溃疡)及其相关细菌。
{"title":"Bacterial infections associated with cutaneous leishmaniasis in Salah Al-Din province, Iraq","authors":"Noor Waleed Al-Alousy,&nbsp;Fatima Shihab Al-Nasiri","doi":"10.1016/j.micpath.2024.107144","DOIUrl":"10.1016/j.micpath.2024.107144","url":null,"abstract":"<div><div>Bacterial co-infection with cutaneous leishmaniasis (CL) can effect on the clinical appearance of lesions and delay the healing process. The pattern of bacterial pathogens involved has rarely been investigated in Iraq. The aim of present study was to identify the bacterial agents contaminating CL and their susceptibility to commonly used antibiotics.</div><div>Four hundred cases of CL were diagnosed in Salah El-Din General Hospital, Iraq. A total of 424 ulcer samples obtained from 400 patients of CL were cultured, and all isolates were diagnosed based on phenotypic characteristics of colonies, bacterial cells and using biochemical tests.</div><div>No bacterial growth appeared in 124 cases (29.25 %) of the total number of examined ulcer samples, whereas 300 cases (70.75 %) were contaminated. Both Gram-positive (<em>Staphylococcus aureus</em>, <em>Staphylococcus epidermidis</em>, <em>Streptococcus pyogenes</em>) and Gram-negative bacterial species (<em>Escherichi coli</em>, <em>Klebsiella</em> spp., <em>Pseudomonas aeruginosa</em>) were present. The infection with <em>S. aureus</em> represented the highest percentage (26.42 %), while <em>Ps. aeruginosa</em> had the lowest percentage (2.83 %) compared with other bacterial infections. The sensitivity of the isolated bacteria associated with CL was tested against a number of antibiotics (Amoxicillin, Ampicillin, Cefixime, Chloramphenlcol, Doxycycline, Tetracycline). Resistance to Amoxicillin, Ampicillin, and Cefixime was generally high. While, Chloramphenicol showed absolute effectiveness against isolated bacteria.</div><div>The results of the current study show that bacterial infections should be considered in diagnosing and treating CL lesions, with Chloramphenicol demonstrating the highest efficiency in treating such bacterial infections. The present study also suggests that hygiene, use of suitable disinfectants, controlling of antibiotic administration and prescription in hospitals and pharmacies must be ensured. In addition, regular surveillance in the endemic area will help control bacterial co-infection and hamper the occurrence of drug-resistant pathogens. The lesion care and management of secondary bacterial infection are essential and anti -leishmanial therapy in CL may be more effective when combined with antibiotics.</div><div>Future molecular studies are needed to identify the species of <em>Leishmania</em> causing CL in Iraq to gain a better understanding of their clinical manifestations (dry or moist ulcers) and their associated bacteria.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"198 ","pages":"Article 107144"},"PeriodicalIF":3.3,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multicenter systematic review of clinical characteristics, diagnostic optimization, and personalized treatment for brain Nocardia infections 脑诺卡菌感染的临床特征、诊断优化和个性化治疗的多中心系统性回顾。
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-22 DOI: 10.1016/j.micpath.2024.107147
Jirao Shen , Bingqian Du , Zhiguo Liu , Ziyu Song , Min Yuan , Xiaotong Qiu , Zhenjun Li
This study provides a systematic review of 512 reported cases of Nocardia brain infections from 2000 to mid-2024. It focuses on analyzing clinical manifestations, radiological findings, bacterial identification methods, and antibiotic resistance patterns. Special attention is given to the differences in outcomes between immunocompromised and non-immunocompromised patients. We also explored personalized treatment approaches by analyzing outcome-related factors through correlation analysis and linear discriminant analysis. Imaging findings commonly showed brain abscesses, lesions, and mass effects, with a high prevalence of antibiotic resistance. Diagnostic methods using conventional microbiological cultures were less effective compared to advanced molecular diagnostics, which enhanced detection accuracy and reduced time to diagnosis. This review also identifies key factors influencing treatment outcomes, including the timely initiation of appropriate antibiotics, particularly the combination of sulfonamides and β-lactams, as well as the importance of surgical intervention. These findings underscore the necessity of improving diagnostic and therapeutic strategies to achieve early diagnosis and personalized treatment.
本研究对 2000 年至 2024 年中期报告的 512 例脑诺卡氏菌感染病例进行了系统回顾。重点分析了临床表现、放射学检查结果、细菌鉴定方法和抗生素耐药性模式。我们特别关注了免疫力低下和非免疫力低下患者的治疗效果差异。我们还通过相关分析和线性判别分析分析了与结果相关的因素,从而探索了个性化治疗方法。影像学检查结果通常显示脑脓肿、病变和肿块效应,抗生素耐药率较高。与先进的分子诊断相比,使用传统微生物培养的诊断方法效果较差,而先进的分子诊断可提高检测准确性并缩短诊断时间。本综述还指出了影响治疗效果的关键因素,包括及时使用适当的抗生素,尤其是磺胺类药物和β-内酰胺类药物的联合应用,以及手术干预的重要性。这些发现强调了改进诊断和治疗策略以实现早期诊断和个性化治疗的必要性。
{"title":"Multicenter systematic review of clinical characteristics, diagnostic optimization, and personalized treatment for brain Nocardia infections","authors":"Jirao Shen ,&nbsp;Bingqian Du ,&nbsp;Zhiguo Liu ,&nbsp;Ziyu Song ,&nbsp;Min Yuan ,&nbsp;Xiaotong Qiu ,&nbsp;Zhenjun Li","doi":"10.1016/j.micpath.2024.107147","DOIUrl":"10.1016/j.micpath.2024.107147","url":null,"abstract":"<div><div>This study provides a systematic review of 512 reported cases of <em>Nocardia</em> brain infections from 2000 to mid-2024. It focuses on analyzing clinical manifestations, radiological findings, bacterial identification methods, and antibiotic resistance patterns. Special attention is given to the differences in outcomes between immunocompromised and non-immunocompromised patients. We also explored personalized treatment approaches by analyzing outcome-related factors through correlation analysis and linear discriminant analysis. Imaging findings commonly showed brain abscesses, lesions, and mass effects, with a high prevalence of antibiotic resistance. Diagnostic methods using conventional microbiological cultures were less effective compared to advanced molecular diagnostics, which enhanced detection accuracy and reduced time to diagnosis. This review also identifies key factors influencing treatment outcomes, including the timely initiation of appropriate antibiotics, particularly the combination of sulfonamides and β-lactams, as well as the importance of surgical intervention. These findings underscore the necessity of improving diagnostic and therapeutic strategies to achieve early diagnosis and personalized treatment.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"198 ","pages":"Article 107147"},"PeriodicalIF":3.3,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Modified lipids from Trypanosoma cruzi amastigotes down-regulate the pro-inflammatory response and increase the expression of alternative activation markers in macrophages 来自克氏锥虫腹吸虫的修饰脂质可下调巨噬细胞的促炎反应并增加替代活化标记物的表达。
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-22 DOI: 10.1016/j.micpath.2024.107140
Federico Nicolas Penas , Emanuel Bott , Alan Brito Carneiro , Sebastián Andrés López , Patricia Torres Bozza , Nora Beatriz Goren , Guadalupe Gimenez , María Laura Belaunzarán
Herein, we analyzed the in vitro effect induced by total lipid extracts from Trypanosoma cruzi amastigotes of RA and K98 strains, which were obtained after overnight incubation (RAinc and K98inc) to mimic phospholipid hydrolytic processes that occurred adjacent to degenerating amastigote nests in tissues of Chagas disease patients. We demonstrated that RAinc and K98inc might possess bioactive lipid molecules with anti-inflammatory bias since they inactivated the NF-κB pathway, in contrast to intact lipids. Moreover, different M1/M2 macrophage phenotype markers of polarization were analyzed by RT-qPCR which evidenced that RAinc and K98inc promoted an increased expression of the M2 markers Arginase-1, IL-10, FIZZ and YM-1, and a decreased expression of iNOS and proinflammatory cytokines IL-6 and TNF-α. All these results indicate the relevant role of T. cruzi in bioactive lipid molecules, deepening thus our understanding of their contribution to immunomodulatory mechanisms as well as to macrophage polarization that occurs during the course of Chagas disease.
在此,我们分析了从RA株和K98株的克鲁斯锥虫非原虫中提取的总脂质所诱导的体外效应,这些总脂质是在过夜培养后获得的(RAinc和K98inc),以模拟恰加斯病患者组织中退化的非原虫巢附近发生的磷脂水解过程。我们证明 RAinc 和 K98inc 可能具有生物活性脂质分子,具有抗炎作用,因为与完整的脂质相比,它们能使 NF-κB 通路失活。此外,通过 RT-qPCR 分析了不同的 M1/M2 巨噬细胞表型极化标志物,结果表明 RAinc 和 K98inc 促进了 M2 标志物精氨酸酶-1、IL-10、FIZZ 和 YM-1 的表达,降低了 iNOS 以及促炎细胞因子 IL-6 和 TNF-α 的表达。所有这些结果都表明了南美锥虫在生物活性脂质分子中的相关作用,从而加深了我们对它们对免疫调节机制以及南美锥虫病病程中发生的巨噬细胞极化所作贡献的理解。
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引用次数: 0
Eco-friendly synthesis of ZnO nanoparticles fabricated using Fioria vitifolia L. and their Biomedical Potentials. 使用 Fioria vitifolia L. 以生态友好方式合成氧化锌纳米粒子及其生物医学潜力。
IF 3.3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2024-11-21 DOI: 10.1016/j.micpath.2024.107139
Mohamed Imath, Jayant Giri, Faruq Mohammad, Chinnasamy Ragavendran, Jameel Al-Tamimi, Hossan Ebaid

The present study aimed to environmentally friendly synthesis of ZnO NPs using Fioria vitifolia leaf extracts which provides a sustainable and green approach for production of NPs. The produced ZnO NPs were evaluated using various spectrum approaches (UV-vis, FTIR XRD, TEM and EDAX). The synthesized ZnO NPs was confirmed by UV-Visible spectroscopy exhibited a peak at 370 nm. SEM imaging revealed a flash-like and needle-like bottom morphology. Fourier-transform infrared spectroscopy (FTIR) analysis detected vibrations corresponding to alcohols, halides, and aromatics functional groups. TEM showed spherical-shaped NPs with an average diameter of 11 nm. XRD analysis exhibited distinct peaks at 2θ values of 31.7°, 34.3°, 36.2°, 47.4°, 56.6°, 62.8°, 66.4°, 67.9°, 69.1°, and 76.8°, corresponding to the crystallographic planes (100), (002), (101), (102), (110), (103), (200), (112), (201), (004), and (202) planes respectively. The antibacterial activity demonstrated significant zones of inhibition against E. coli (17±0.6 mm) and S. aureus (23.7±0.5 mm), and inhibition of biofilm formation in S. aureus and C. albicans. Additionally, S. mutans exhibited the highest sensitivity to the minimum inhibitory concentration (MIC) of ZnO NPs, with complete inhibition occurring at 7.5 μg/mL. Furthermore, antioxidant DPPH assays exhibited IC50 values of 42 μg/mL. Additionally, the anti-inflammatory properties of ZnO NPs of F. vitifolia were evaluated in-vitro using models utilizing the human red blood cells (HRBC) membrane stabilization method (MSM), and it was shown to have an MSM of 83.87% at 250 μg/mL. Furthermore, ZnO NPs exhibited anticancer activity against the MDA-MB-231 breast cancer cell line with an IC50 value of 35.50 μg/mL. Toxicological evaluation of FV-ZnO nanoparticles in zebrafish (Danio rerio) embryos indicated low toxicity at maximum concentration. These is first findings suggest that ZnO NPs synthesized from F. vitifolia leaf extracts possess significant antibacterial, antioxidant, anti-inflammatory, and anticancer properties. Additionally, their low toxicity in zebrafish embryos makes them suitable for further development in antimicrobial therapies with minimal side effects, offering a sustainable, biocompatible solution to tackle multidrug-resistant microbial infections.

本研究旨在利用 Fioria vitifolia 叶提取物合成环境友好型 ZnO NPs,为生产 NPs 提供了一种可持续的绿色方法。使用各种光谱方法(紫外可见光、傅立叶变换红外光谱、X射线衍射、TEM和EDAX)对所制备的氧化锌氮氧化物进行了评估。紫外可见光谱证实合成的 ZnO NPs 在 370 纳米处出现峰值。扫描电镜成像显示了闪烁状和针状的底部形态。傅立叶变换红外光谱(FTIR)分析检测到与醇、卤化物和芳香族官能团相对应的振动。TEM 显示出平均直径为 11 纳米的球形 NPs。XRD 分析显示,在 31.7°、34.3°、36.2°、47.4°、56.6°、62.8°、66.4°、67.9°、69.1° 和 76.8°的 2θ 值处有明显的峰值,分别对应于结晶平面(100)、(002)、(101)、(102)、(110)、(103)、(200)、(112)、(201)、(004)和(202)平面。抗菌活性显示了对大肠杆菌(17±0.6 毫米)和金黄色葡萄球菌(23.7±0.5 毫米)的显著抑制区,以及对金黄色葡萄球菌和白喉杆菌生物膜形成的抑制作用。此外,金黄色葡萄球菌对 ZnO NPs 的最小抑菌浓度 (MIC) 表现出最高的敏感性,在 7.5 μg/mL 时可完全抑制。此外,抗氧化 DPPH 试验的 IC50 值为 42 μg/mL。此外,还利用人体红血细胞(HRBC)膜稳定法(MSM)模型对 F. vitifolia ZnO NPs 的抗炎特性进行了体外评估,结果表明在 250 μg/mL 时,其 MSM 值为 83.87%。此外,氧化锌纳米粒子对 MDA-MB-231 乳腺癌细胞系具有抗癌活性,IC50 值为 35.50 μg/mL。FV-ZnO 纳米粒子在斑马鱼(Danio rerio)胚胎中的毒理学评估表明,在最大浓度下毒性较低。这些研究结果首次表明,从F. vitifolia叶提取物中合成的氧化锌纳米粒子具有显著的抗菌、抗氧化、抗炎和抗癌特性。此外,它们在斑马鱼胚胎中的低毒性使其适合进一步开发副作用最小的抗菌疗法,为解决耐多药微生物感染问题提供了一种可持续的、生物兼容的解决方案。
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引用次数: 0
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Microbial pathogenesis
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