Dataset Information

New Delhi metallo-?-lactamase-1-producing Klebsiella pneumoniae isolates in hospitalized patients in Kashan, Iran.

ABSTRACT: Background and Objectives:New Delhi metallo-ß-lactamase (NDM) is a newly emerging metallo-ß-lactamases, which can destroy all ?-lactams including carbapenems. Therefore, this study aimed at evaluating New Delhi metallo-ß-lactamase-1-production in clinical isolates of Klebsiella pneumoniae in Kashan, Iran. Materials and Methods:In a cross-sectional study, 181 K. pneumoniae isolates were collected from clinical samples of patients, who referred to Shahid Beheshi hospital in Kashan during November 2013 and October 2014. Antimicrobial susceptibility patterns were determined using disk diffusion method, according to CLSI guidelines. Metallo-ß-lactamase (MBL) production was identified among imipenem-resistant K. pneumoniae isolates using imipenem-EDTA double disk synergy test (EDTA-IMP DDST). PCR method and sequencing were used to detect integron Class 1 and blaNDM-1 gene. Statistical analyses were performed using SPSS software Version 16. Results:Of the 181 K. pneumoniae isolates, 36 (19.9 %) were imipenem-resistant strains. A total of 28 out of 36 (77.7%) imipenem-resistant K. pneumoniae isolates were identified as MBL producer strains. Also, 150 (82.9%) K. pneumoniae isolates carried intI1 gene, and 20 (11.1%) K. pneumoniae isolates harbored blaNDM-1 gene. Conclusion:Our study revealed a high frequency of MBL production and the presence of blaNDM-1 among K. pneumoniae strains, especially among hospitalized patients, which is alarming. Moreover, the presence of Class 1 integrons in all multi-drug resistant K. pneumoniae isolates highlights the risk of rapid spread of the resistance genes, especially in clinical settings.

SUBMITTER: Firoozeh F

PROVIDER: S-EPMC5748447 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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New Delhi metallo-β-lactamase-1-producing <i>Klebsiella pneumoniae</i> isolates in hospitalized patients in Kashan, Iran.

Firoozeh Farzaneh F Mahluji Zeinab Z Shams Ehsaneh E Khorshidi Ahmad A Zibaei Mohammad M

Iranian journal of microbiology 20171001 5

<h4>Background and objectives</h4>New Delhi metallo-ß-lactamase (NDM) is a newly emerging metallo-ß-lactamases, which can destroy all β-lactams including carbapenems. Therefore, this study aimed at evaluating New Delhi metallo-ß-lactamase-1-production in clinical isolates of <i>Klebsiella pneumoniae</i> in Kashan, Iran.<h4>Materials and methods</h4>In a cross-sectional study, 181 <i>K. pneumoniae</i> isolates were collected from clinical samples of patients, who referred to Shahid Beheshi hospit ...[more]

PMID: 29296273

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Project description:Polymyxins are last-line antibiotics employed against multidrug-resistant (MDR) Klebsiella pneumoniae. Worryingly, polymyxin resistance is rapidly on the rise globally. Polymyxins initially target lipid A of lipopolysaccharides (LPSs) in the cell outer membrane (OM), causing disorganization and cell lysis. While most studies focus on how genetic variations confer polymyxin resistance, the mechanisms of membrane remodeling and metabolic changes in polymyxin-resistant strains remain unclear, thus hampering the development of effective therapies to treat severe K. pneumoniae infections. In the present study, lipid A profiling, OM lipidomics, genomics, and metabolomics were integrated to elucidate the global mechanisms of polymyxin resistance and metabolic adaptation in a polymyxin-resistant strain (strain S01R; MIC of >128 mg/L) obtained from K. pneumoniae strain S01, a polymyxin-susceptible (MIC of 2 mg/L), New Delhi metallo-β-lactamase (NDM)-producing MDR clinical isolate. Genomic analysis revealed a novel in-frame deletion at position V258 of PhoQ in S01R, potentially leading to lipid A modification with 4-amino-4-deoxy-l-arabinose (L-Ara4N) despite the absence of polymyxin B. Comparative metabolomic analysis revealed slightly elevated levels of energy production and amino acid metabolism in S01R compared to their levels in S01. Exposure to polymyxin B (4 mg/L for S01 and 512 mg/L for S01R) substantially altered energy, nucleotide, and amino acid metabolism and resulted in greater accumulation of lipids in both strains. Furthermore, the change induced by polymyxin B treatment was dramatic at both 1 and 4 h in S01 but only significant at 4 h in S01R. Overall, profound metabolic adaptation was observed in S01R following polymyxin B treatment. These findings contribute to our understanding of polymyxin resistance mechanisms in problematic NDM-producing K. pneumoniae strains and may facilitate the discovery of novel therapeutic targets. IMPORTANCE Antimicrobial resistance (AMR) is a major threat to global health. The emergence of resistance to the polymyxins that are the last line of defense in so-called Gram-negative "superbugs" has further increased the urgency to develop novel therapies. There are frequent outbreaks of K. pneumoniae infections in hospitals being reported, and polymyxin usage is increasing remarkably. Importantly, the polymyxin-resistant K. pneumoniae strains are imposing more severe consequences to health systems. Using metabolomics, lipid A profiling, and outer membrane lipidomics, our findings reveal (i) changes in the pentose phosphate pathway and amino acid and nucleotide metabolism in a susceptible strain following polymyxin treatment and (ii) how cellular metabolism, lipid A modification, and outer membrane remodeling were altered in K. pneumoniae following the acquisition of polymyxin resistance. Our study provides, for the first time, mechanistic insights into metabolic responses to polymyxin treatment in a multidrug-resistant, NDM-producing K. pneumoniae clinical isolate with acquired polymyxin resistance. Overall, these results will assist in identifying new therapeutic targets to combat and prevent polymyxin resistance.

Dataset Information

New Delhi metallo-?-lactamase-1-producing Klebsiella pneumoniae isolates in hospitalized patients in Kashan, Iran.

Publications

New Delhi metallo-β-lactamase-1-producing <i>Klebsiella pneumoniae</i> isolates in hospitalized patients in Kashan, Iran.

Similar Datasets

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