Displaying publications 41 - 50 of 50 in total

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  1. Fulltext MgrB Mutations and Altered Cell Permeability in Colistin Resistance in Klebsiella pneumoniae
    Yap PS, Cheng WH, Chang SK, Lim SE, Lai KS
    Cells, 2022 Sep 26;11(19).
    PMID: 36230959 DOI: 10.3390/cells11192995
    There has been a resurgence in the clinical use of polymyxin antibiotics such as colistin due to the limited treatment options for infections caused by carbapenem-resistant Enterobacterales (CRE). However, this last-resort antibiotic is currently confronted with challenges which include the emergence of chromosomal and plasmid-borne colistin resistance. Colistin resistance in Klebsiella pneumoniae is commonly caused by the mutations in the chromosomal gene mgrB. MgrB spans the inner membrane and negatively regulates PhoP phosphorylation, which is essential for bacterial outer membrane lipid biosynthesis. The present review intends to draw attention to the role of mgrB chromosomal mutations in membrane permeability in K. pneumoniae that confer colistin resistance. With growing concern regarding the global emergence of colistin resistance, deciphering physical changes of the resistant membrane mediated by mgrB inactivation may provide new insights for the discovery of novel antimicrobials that are highly effective at membrane penetration, in addition to finding out how this can help in alleviating the resistance situation.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  2. Detection and factors associated with tuberculosis and rifampicin resistance among presumptive patients at the Thailand-Myanmar border
    Klayut W, Rudeeaneksin J, Srisungngam S, Bunchoo S, Bhakdeenuan P, Phetsuksiri B, et al.
    Trop Biomed, 2022 Dec 01;39(4):483-488.
    PMID: 36602205 DOI: 10.47665/tb.39.4.001
    Tuberculosis (TB) continues to be a major public health problem in Thailand and many countries. Endemic TB and outbreaks of TB drug resistance in the borderlands are particularly important. The Thailand-Myanmar border has extensive cross-border travel that may accelerate TB's spread. This cross-sectional study aimed to determine the frequency and factors associated with TB, and rifampicinresistant TB (RR-TB) among presumptive tuberculosis patients in Mae Sot Hospital. Sputum was processed by microscopic examination and Xpert MTB/RIF assay. Laboratory results and socio-demographic characteristics were collected and analyzed. Univariate and multivariate analyses were performed to assess the association of the risk factors with TB and RR-TB. The significant variables at p-values < 0.05 in univariate analysis were selected for multivariate analysis. Of 365 presumptive patients enrolled, 244 (66.85%) were males and 199 (54.52%) were Burmese. Of these, 314 (86.03%) were registered as new cases and 183 (50.14%) worked as laborers. Sputum microscopy was positive in 132 (36.16%) cases. Based on Xpert MTB/RIF, the frequency of TB was 136 (37.26%) and RR-TB was 15 (11.03%). TB was more common in males than females. The majority of the cases belonged to the 26-50-year-old age group and migrant workers. In RR-TB detection, the rpoB mutations covered by probe E were the most frequently observed. Sequencing showed that the most highly mutated codon was codon 531 and Ser531Thr was the most common mutation. For risk factor analysis, working as laborers was significantly (p-value < 0.05) associated with TB (aOR 2.83; 95% CI 1.43-5.63) and previously treated cases were significantly associated with RR-TB (aOR 12.33; 95% CI 2.29-66.49). The high frequency of TB and RR-TB in migrants highlights the problem and factors associated with TB at the border and the need for efforts in TB control programs in this setting.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  3. Fulltext Molecular detection and antimicrobial resistance profiles of Extended-Spectrum Beta-Lactamase (ESBL) producing Escherichia coli in broiler chicken farms in Malaysia
    Lemlem M, Aklilu E, Mohammed M, Kamaruzzaman F, Zakaria Z, Harun A, et al.
    PLoS One, 2023;18(5):e0285743.
    PMID: 37205716 DOI: 10.1371/journal.pone.0285743
    Antimicrobial resistance is one of the major public health threats globally. This challenge has been aggravated with the overuse and misuse of antibiotics in food animals and humans. The present study aimed to investigate the prevalence of Extended-Spectrum β-lactamase (ESBL) genes in Escherichia coli (E. coli) isolated from broiler chickens in Kelantan, Malaysia. A total of 320 cloacal swabs were collected from farms in different districts of Kelantan and were analyzed using routine bacteriology, antimicrobial susceptibility test, and molecular techniques for further identification and characterization of ESBL encoding genes. Based on PCR detection for the E. coli species-specific Pho gene, 30.3% (97/320) of isolates were confirmed as E. coli, and 84.5% (82/97) of the isolates were positive for at least one ESBL gene. Majority of the isolates, 62.9% (61/97) were harboring blaCTX-M followed by 45.4% (44/97) of blaTEM genes, while 16.5% (16/97) of the isolates were positive for both mcr-1 and ESBL genes. Overall, 93.8% (90/97) of the E. coli were resistant to three or more antimicrobials; indicating that the isolates were multi-drug resistance. 90.7% of multiple antibiotic resistance (MAR) index value greater than 0.2, would also suggest the isolates were from high-risk sources of contamination. The MLST result shows that the isolates are widely diverse. Our findings provide insight into the alarmingly high distribution of antimicrobial resistant bacteria, mainly ESBL producing E. coli in apparently healthy chickens indicating the role of food animals in the emergence and spread of antimicrobial resistance, and the potential public health threats it may pose.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  4. Antibiotic resistance and determination of resistant genes among cockle (Anadara granosa) isolates of Vibrio alginolyticus
    Shahimi S, Elias A, Abd Mutalib S, Salami M, Fauzi F, Mohd Zaini NA, et al.
    Environ Sci Pollut Res Int, 2021 Aug;28(32):44002-44013.
    PMID: 33846919 DOI: 10.1007/s11356-021-13665-4
    A total of 24 strains of Vibrio alginolyticus were isolated from cockles (Anadara granosa) and identified for VibA and gyrB genes. All V. alginolyticus isolates were then tested against nine different antibiotics. In this study, the highest percentage of antibiotic resistance was obtained against penicillin (37.50%), followed by ampicillin, vancomycin (12.50%) and erythromycin (8.33%). All of V. alginolyticus isolates were susceptible against streptomycin, kanamycin, tetracycline, chloramphenicol and sulfamethoxazole. Polymerase chain reaction (PCR) assay has confirmed the presence of four antibiotic resistance genes of penicillin (pbp2a), ampicillin (blaOXA), erythromycin (ermB) and vancomycin (vanB). Out of 24 V. alginolyticus isolates, 2 isolates possessed the tdh-related hemolysin (trh) (strains VA15 and VA16) and none for the thermostable direct hemolysin (tdh) gene. Both strains of the tdh-related hemolysin (trh) were susceptible to all antibiotics tested. The multiple antibiotic resistance (MAR) index ranging between 0.2 and 0.3 with 5 antibiograms (A1-A5) was observed. Combination of enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) and antibiotic resistance indicated 18 genome types which showed genetic heterogeneity of those V. alginolyticus isolates. The results demonstrated the presence of V. alginolyticus strain found in cockles can be a potential risk to consumers and can contribute to the deterioration of human health in the study area. Thus, it is essential for local authority to provide the preventive measures in ensuring the cockles are safe for consumption.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  5. Fulltext Do the clonally different Escherichia coli isolates causing different infections in a HIV positive patient affect the selection of antibiotics for their treatment?
    Rameshkumar MR, Arunagirinathan N, Swathirajan CR, Vignesh R, Balakrishnan P, Solomon SS
    Indian J Med Res, 2018 09;148(3):341-344.
    PMID: 30425226 DOI: 10.4103/ijmr.IJMR_730_17
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  6. Metabonomics reveals an alleviation of fitness cost in resistant E. coli competing against susceptible E. coli at sub-MIC doxycycline
    Wen X, Cao J, Mi J, Huang J, Liang J, Wang Y, et al.
    J Hazard Mater, 2021 03 05;405:124215.
    PMID: 33109407 DOI: 10.1016/j.jhazmat.2020.124215
    High concentrations of antibiotics may induce bacterial resistance mutations and further lead to fitness costs by reducing growth of resistant bacteria. However, antibiotic concentrations faced by bacteria are usually low in common environments, which leads to questions about how resistant bacteria with fitness costs regulate metabolism to coexist or compete with susceptible bacteria during sublethal challenge. Our study revealed that a low proportion (< 15%) of resistant bacteria coexisted with susceptible bacteria due to the fitness cost without doxycycline. However, the cost for the resistant strain decreased at a doxycycline concentration of 1 mg/L and even disappeared when the doxycycline concentration was 2 mg/L. Metabonomics analysis revealed that bypass carbon metabolism and biosynthesis of secondary metabolites were the primary metabolic pathways enriching various upregulated metabolites in resistant bacteria without doxycycline. Moreover, the alleviation of fitness cost for resistant bacteria competed with susceptible bacteria at 1 mg/L doxycycline was correlated with the downregulation of the biomarkers pyruvate and pilocarpine. Our study offered new insight into the metabolic mechanisms by which the fitness cost of resistant mutants was reduced at doxycycline concentrations as low as 1 mg/L and identified various potential metabolites to limit the spread of antimicrobial resistance in the environment.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  7. A stop-gain mutation in sigma factor SigH (MAB_3543c) may be associated with tigecycline resistance in Mycobacteroides abscessus
    Lee CL, Ng HF, Ngeow YF, Thaw Z
    J Med Microbiol, 2021 Jul;70(7).
    PMID: 34236301 DOI: 10.1099/jmm.0.001378
    Introduction. Tigecycline is currently acknowledged to be one of the most effective antibiotics against infections caused by Mycobacteroides abscessus.Gap statement. The genetic determinants of tigecycline resistance in M. abscessus are not well understood.Aim. In this study, we characterized a tigecycline-resistant M. abscessus mutant, designated CL7, to identify the potential resistance mechanism.Methodology. CL7 was characterized using antimicrobial susceptibility testing, whole-genome sequencing, PCR and RT-qPCR. For biological verification, gene overexpression assays were carried out.Results. Whole-genome sequencing and the subsequent gene overexpression assays showed that CL7 harboured a stop-gain mutation in MAB_3543 c, which may be responsible for the tigecycline resistance phenotype. This gene encodes an orthologue of SigH, which is involved in the positive regulation of physiological stress response and is negatively regulated by the RshA anti-sigma factor in Mycobacterium tuberculosis. We hypothesized that the MAB_3543 c mutation may disrupt the interaction between SigH and RshA (MAB_3542 c). RT-qPCR analyses revealed the upregulation of MAB_3543 c and other key stress response genes, which has previously been shown to be a hallmark of SigH-RshA bond disruption and tigecycline resistance.Conclusion. The MAB_3543c mutation may represent a novel determinant of tigecycline resistance in M. abscessus. The findings of this study will hopefully contribute to our knowledge of potential tigecycline resistance mechanisms in M. abscessus, which may lead to better diagnostics and treatment modalities in the future.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics*
  8. Fulltext The challenges of designing a benchmark strategy for bioinformatics pipelines in the identification of antimicrobial resistance determinants using next generation sequencing technologies
    Angers-Loustau A, Petrillo M, Bengtsson-Palme J, Berendonk T, Blais B, Chan KG, et al.
    F1000Res, 2018;7.
    PMID: 30026930 DOI: 10.12688/f1000research.14509.2
    Next-Generation Sequencing (NGS) technologies are expected to play a crucial role in the surveillance of infectious diseases, with their unprecedented capabilities for the characterisation of genetic information underlying the virulence and antimicrobial resistance (AMR) properties of microorganisms.  In the implementation of any novel technology for regulatory purposes, important considerations such as harmonisation, validation and quality assurance need to be addressed.  NGS technologies pose unique challenges in these regards, in part due to their reliance on bioinformatics for the processing and proper interpretation of the data produced.  Well-designed benchmark resources are thus needed to evaluate, validate and ensure continued quality control over the bioinformatics component of the process.  This concept was explored as part of a workshop on "Next-generation sequencing technologies and antimicrobial resistance" held October 4-5 2017.   Challenges involved in the development of such a benchmark resource, with a specific focus on identifying the molecular determinants of AMR, were identified. For each of the challenges, sets of unsolved questions that will need to be tackled for them to be properly addressed were compiled. These take into consideration the requirement for monitoring of AMR bacteria in humans, animals, food and the environment, which is aligned with the principles of a "One Health" approach.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics*
  9. Mutations in Genes Encoding 23S rRNA and FadD32 May be Associated with Linezolid Resistance in Mycobacteroides abscessus
    Ng HF, Ngeow YF
    Microb Drug Resist, 2023 Feb;29(2):41-46.
    PMID: 36802272 DOI: 10.1089/mdr.2022.0068
    Linezolid is one of the antibiotics used to treat the Mycobacteroides abscessus infection. However, linezolid-resistance mechanisms of this organism are not well understood. The objective of this study was to identify possible linezolid-resistance determinants in M. abscessus through characterization of step-wise mutants selected from a linezolid-susceptible strain, M61 (minimum inhibitory concentration [MIC]: 0.25 mg/L). Whole-genome sequencing and subsequent PCR verification of the resistant second-step mutant, A2a(1) (MIC: >256 mg/L), revealed three mutations in its genome, two of which were found in the 23S rDNA (g2244t and g2788t) and another one was found in a gene encoding the fatty-acid-CoA ligase FadD32 (c880t→H294Y). The 23S rRNA is the molecular target of linezolid and mutations in this gene are likely to contribute to resistance. Furthermore, PCR analysis revealed that the c880t mutation in the fadD32 gene first appeared in the first-step mutant, A2 (MIC: 1 mg/L). Complementation of the wild-type M61 with the pMV261 plasmid carrying the mutant fadD32 gene caused the previously sensitive M61 to develop a reduced susceptibility to linezolid (MIC: 1 mg/L). The findings of this study uncovered hitherto undescribed mechanisms of linezolid resistance in M. abscessus that may be useful for the development of novel anti-infective agents against this multidrug-resistant pathogen.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics
  10. Global spread of the linezolid-resistant Enterococcus faecalis ST476 clonal lineage carrying optrA
    Brenciani A, Cinthi M, Coccitto SN, Massacci FR, Albini E, Cucco L, et al.
    J Antimicrob Chemother, 2024 Apr 02;79(4):846-850.
    PMID: 38366373 DOI: 10.1093/jac/dkae039
    OBJECTIVES: To investigate the global distribution of an optrA-harbouring linezolid-resistant Enterococcus faecalis ST476 clonal lineage.

    METHODS: Comprehensive searches of the NCBI database were performed to identify published peer-reviewed articles and genomes of E. faecalis ST476. Each genome was analysed for resistome, virulome, OptrA variant and optrA genetic contexts. A phylogenetic comparison of ST476 genomes with publicly available genomes of other STs was also performed.

    RESULTS: Sixty-six E. faecalis ST476 isolates from 15 countries (China, Japan, South Korea, Austria, Denmark, Spain, Czech Republic, Colombia, Tunisia, Italy, Malaysia, Belgium, Germany, United Arab Emirates and Switzerland) mainly of human and animal origin were identified. Thirty available ST476 genomes compared with genomes of 591 STs indicated a progressive radiation of E. faecalis STs starting from ST21. The closest ancestral node for ST476 was ST1238. Thirty E. faecalis ST476 genomes exhibited 3-916 SNP differences. Several antimicrobial resistance and virulence genes were conserved among the ST476 genomes. The optrA genetic context exhibited a high degree of or complete identity to the chromosomal transposon Tn6674. Only three isolates displayed an optrA-carrying plasmid with complete or partial Tn6674. The WT OptrA protein was most widespread in the ST476 lineage.

    CONCLUSIONS: Linezolid-resistant optrA-carrying E. faecalis of the clonal lineage ST476 is globally distributed in human, animal and environmental settings. The presence of such an emerging clone can be of great concern for public health. Thus, a One Health approach is needed to counteract the spread and the evolution of this enterococcal clonal lineage.

    Matched MeSH terms: Drug Resistance, Bacterial/genetics
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