Microbial drug resistance最新文献

Background: The increased incidence of infections due to multidrug-resistant Gram-negative bacteria has led to the renewed interest in the use of 'forgotten' antibiotics such as colistin. In this work, we studied the chromosomal colistin resistance mechanisms among laboratory-induced colistin-resistant Escherichia coli isolates. Methods: Three colistin-susceptible (ColS) clinical isolates of E. coli assigning to ST131, ST405, and ST361 were exposed to successively increasing concentrations of colistin. The nucleotide sequences of pmrA, pmrB, pmrD, phoP, phoQ, and mgrB genes were determined. The fitness burden associated with colistin resistance acquisition was determined by measuring the in vitro growth rate. Results: Colistin resistance induction resulted in 16-64 times increase in colistin MICs in mutants (n = 8) compared with parental isolates. Analysis of chromosomal genes in colistin-resistant mutants compared with those of ColS ancestors revealed genetic alterations confined to PmrAB two-component system and included PmrA G53R/R81S/L105P and PmrB E121K/E121A/A159P/A159V/G302E changes. The PmrB E121 was found as a critical position for colistin resistance development being altered in three mutants with different ancestors. The acquired colistin-resistance phenotype was stable following 10 consecutive passages in the absence of selective pressure of colistin and it did not alter the susceptibility of mutants to other antimicrobial agents. All mutants exhibited growth rates similar to their respective ColS ancestors, except for one isolate, which revealed a significant growth defect. Conclusion: Our results revealed that colistin resistance in E. coli was more related to PmrAB alterations, which did not impose a fitness cost in most cases.

The emergence of carbapenemase-producing Klebsiella pneumoniae poses a substantial risk to public health. It is essential to comprehend the influence of carbapenemase on the virulence characteristics of K. pneumoniae in order to devise successful strategies for combating these infections. In this study, we explored the distribution disparity of virulence determinants between carbapenemase-producing (CP-Kp, n = 52) and carbapenemase-nonproducing (CN-Kp, n = 43) isolates. The presence of carbapenemases was detected via the modified carbapenem inactivation method and confirmed by PCR. The New Delhi metallo-β-lactamase (bla_NDM) and Oxacillinase-48-like (bla_OXA-48-like) genes were the most prevalent (94.23% and 76.92%, respectively) in CP-Kp isolates. Coexistence of bla_NDM and bla_OXA-48-like was observed in 71.15% of isolates, whereas 5.77% coharbored bla_NDM and bla_KPC. PCR analysis revealed the presence of several virulence genes, including adhesins (fimH, 92.63%, mrkD, 97.89%), capsule-associated virulence (uge, 90.53%), the K2 capsule serotype (k2, 6.32%), the iron acquisition system (kfu, 23.16%), and the regulator of mucoid phenotype (rmpA, 28.42%). A significantly higher prevalence of rmpA was detected in the CP-Kp compared with the CN-Kp (24/52 vs. 3/43, p < 0.0001), indicating a potential association between rmpA and carbapenemase acquisition. In addition, the majority of rmpA (22/24) positive isolates in the CP-Kp isolates coharbored bla_NDM and either bla_OXA-48-like or bla_KPC.

The study determined the prevalence, antimicrobial resistant (AMR) determinants, and genetic characteristics of Escherichia coli and Klebsiella pneumoniae isolates from patients with diabetic foot infection (DFI) in a Tunisian hospital. A total of 26 Escherichia spp. and Klebsiella spp. isolates were recovered and identified by MALDI-TOF-MS. Antimicrobial susceptibility testing, the detection of AMR determinants and Shiga-like toxin genes, phylogenetic grouping, and molecular typing were performed. Twelve E. coli, 10 K. pneumoniae, 3 K. oxytoca, and 1 E. hermanii were isolated. A multidrug-resistant phenotype was detected in 65.4% of the isolates. About 30.8% of isolates were extended-spectrum β-lactamase (ESBL) producers and mainly carried bla_CTX-M-15 and bla_CTX-M-14 genes. One bla_NDM-1-producing K. pneumoniae-ST1 strain was identified. Class 1 integrons were detected in 11 isolates and 5 gene cassette arrangements were noted: dfrA1+aadA1 (n = 1), dfrA12+aadA2 (n = 3), and dfrA17+aadA5 (n = 1). Other non-β-lactam resistance genes detected were as follows (number of isolates): aac(3')-II (3), aac(6')-Ib-cr(8), qnrB (2), qnrS (4), cmlA (2), floR (4), sul1 (11), sul2 (11), and sul3 (2). The phylogroup B1 was the most frequent (41.7%) among E. coli, and two ESBL-producing isolates corresponded to the ST131-B2 lineage. The ESBL- and carbapenemase-producing Enterobacteriaceae in DFIs are described for the first time in Tunisia.

The aim of this study was to evaluate the phenotypic and genotypic responses of Salmonella Typhimurium ATCC 19585 (ST) and Staphylococcus aureus KACC 13236 (SA) preadapted to sublethal concentrations of lactic acid (LA) and sodium chloride (NaCl) for 48 hr at 37°C, followed by re-exposure to lethal concentrations of LA and NaCl for 24 hr at 37°C. ST and SA treated in a sequential and ordered manner with LA and NaCl were assigned as LA-LA, LA-NaCl, NaCl-LA, and NaCl-NaCl. The treatments, LA-LA, LA-NaCl, NaCl-LA, and NaCl-NaCl, were evaluated by antimicrobial susceptibility, bacterial fluctuation, relative fitness, zeta potential, and gene expression. The MIC_t/MIC_c ratios of LA, NaCl, CIP, GEN, and TET against ST treated with LA-LA were 1.0 to 0.8, 0.8, 0.3, 0.4, and 0.5, respectively. The MIC_t/MIC_c ratios of NaCl, CIP, GEN, and TET were between 0.5-0.8 for SA treated with LA-LA. ST treated with LA-LA and SA treated with LA-NaCl exhibited the highest coefficient of variance. The lowest relative fitness was observed at ST treated with LA-LA (0.5). ST and SA treated with LA-LA showed the lowest zeta potential. The transporter-, toxin-antitoxin system-, chaperone protein-, and SOS response-related genes were suppressed at ST and SA treated with LA-LA. The transporter-, toxin-antitoxin system-, and chaperone protein-related genes were overexpressed in SA treated with LA-NaCl, NaCl-LA, and NaCl-NaCl. The results suggest that ST and SA treated with LA-LA, LA-NaCl, NaCl-LA, and NaCl-NaCl could induce collateral sensitivity and cross-resistance.

Little is known about the characteristics of uropathogenic Escherichia coli (UPEC) associated with recurrent urinary tract infections (RUTIs). The present study aimed to analyze the phenotypic antimicrobial resistance of recurrent UPEC isolates attributable to either relapse or reinfection. A total of 140 E. coli strains were isolated from 70 outpatients with RUTIs. All isolates were analyzed by random amplified polymorphic DNA-polymerase chain reaction to evaluate genetic similarity between the first and second isolates. We found that 64.2% (45/70) of outpatients had a relapse with the primary infecting E. coli strain and 35.7% (25/70) had reinfection with a new E. coli strain. Compared with reinfecting strains, relapse UPEC isolates exhibited much higher antimicrobial resistance; 89% of these isolates were multidrug-resistant and 46.6% were extended-spectrum β-lactamase producers. Our study provides evidence that RUTIs are mainly driven by the persistence of the original strain in the host (relapses) despite appropriate antibiotic treatments, and only RUTIs attributed to relapses seem to favor multidrug resistance in UPEC isolates.

Invasive fungal infections in humans with compromised immune systems are the primary cause of morbidity and mortality, which is becoming more widely acknowledged. Amphotericin B (AmB) is one of the antifungal drugs used to treat such infections. AmB binds with plasma membrane ergosterol, inducing cellular ions to leak and causing cell death. Reduction in ergosterol content and modification of cell walls have been described as AmB resistance mechanisms. In addition, when the sphingolipid level is decreased, the cell becomes more susceptible to AmB. Previously, PDR16, a gene that encodes phosphatidylinositol transfer protein in Saccharomyces cerevisiae, was shown to enhance AmB resistance upon overexpression. However, the mechanism of PDR16-mediated AmB resistance is not clear. Here, in this study, it was discovered that a plasma membrane proteolipid 3 protein encoded by PMP3 is essential for PDR16-mediated AmB resistance. PDR16-mediated AmB resistance does not depend on ergosterol, but a functional sphingolipid biosynthetic pathway is required. Additionally, PMP3-mediated alteration in membrane integrity abolishes PDR16 mediated AmB resistance, confirming the importance of PMP3 in the PDR16 mediated AmB resistance.

Candidiasis is a common fungal infection caused by Candida species, with Candida albicans being the most prevalent. Resistance to azole drugs, commonly used to treat Candida infections, poses a significant challenge. Transcriptional activator candidate 1 (TAC1) gene has emerged as a key player in regulating drug resistance in C. albicans. This review explores the structure and function of the TAC1 gene and its role in azole resistance. This gene encodes a transcription factor that controls the expression of genes involved in drug resistance, such as efflux pump genes (CDR1, CDR2, and MDR1) and ERG11. Mutations in TAC1 can increase these genes' expression and confer resistance to azoles. Various TAC1 gene mutations, mostly gain-of-function mutations, have been identified, which upregulate CDR1 and CDR2 expression, resulting in azole resistance. Understanding the mechanisms of azole resistance mediated by the TAC1 gene is crucial for the strategies in the effective antifungal development pipeline.