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High abundance of the colistin resistance gene mcr-1 in chicken gut-bacteria in Bangladesh.

ABSTRACT: Colistin is considered a last-resort reserved drug for the treatment of critical human infections by Gram-negative bacteria. Phenotypic colistin-resistance is strongly associated with plasmid-mediated mobile colistin resistance (mcr) genes. The mcr-bearing Enterobacteriaceae have been detected in many countries from environments, animals, and humans. This study investigated phenotypic colistin-resistance and the distribution of mcr-1, mcr-2, mcr-3, mcr-4, and mcr-5 genes in chicken-gut bacteria in Bangladesh. Bacteria were isolated from poultry- and native-chicken droppings, and their susceptibilities to colistin were determined by agar dilution and E-test minimal inhibitory concentration (MIC) measurements. Multiplex polymerase chain reactions detected mcr-1 to mcr-5 genes. Overall, 61.7% (92/149) of the isolates showed colistin resistance by agar dilution assessment (MIC?>?2.0 ?g/mL). The phenotypic resistance was observed considerably higher in poultry-chicken isolates (64.6%, 64/99) than in native-chicken isolates (56%, 28/50; p?=?0.373). All the resistant isolates showed MIC levels between >?2 and >?128 ?g/mL. The mcr-genes (mcr-1and mcr-2 combined) were detected more in poultry gut bacteria (36.4%) than native-chicken isolates (20%, p?=?0.06). Despite bacteria sources, mcr-genes appeared to be significantly associated with phenotypic colistin-resistance phenomena (p?

SUBMITTER: Islam S

PROVIDER: S-EPMC7560609 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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High abundance of the colistin resistance gene mcr-1 in chicken gut-bacteria in Bangladesh.

Islam Salequl S Urmi Umme Laila UL Rana Masud M Sultana Fahmida F Jahan Nusrat N Hossain Billal B Iqbal Samiul S Hossain Md Moyazzem MM Mosaddek Abu Syed Md ASM Nahar Shamsun S

Scientific reports 20201014 1

Colistin is considered a last-resort reserved drug for the treatment of critical human infections by Gram-negative bacteria. Phenotypic colistin-resistance is strongly associated with plasmid-mediated mobile colistin resistance (mcr) genes. The mcr-bearing Enterobacteriaceae have been detected in many countries from environments, animals, and humans. This study investigated phenotypic colistin-resistance and the distribution of mcr-1, mcr-2, mcr-3, mcr-4, and mcr-5 genes in chicken-gut bacteria ...[more]

PMID: 33057111

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Project description:Antibiotic resistance is a prevalent problem in public health worldwide. In general, the carbapenem β-lactam antibiotics are considered a final resort against lethal infections by multidrug-resistant bacteria. Colistin is a cationic polypeptide antibiotic and acts as the last line of defense for treatment of carbapenem-resistant bacteria. Very recently, a new plasmid-borne colistin resistance gene, mcr-2, was revealed soon after the discovery of the paradigm gene mcr-1, which has disseminated globally. However, the molecular mechanisms for MCR-2 colistin resistance are poorly understood. Here we show a unique transposon unit that facilitates the acquisition and transfer of mcr-2 Evolutionary analyses suggested that both MCR-2 and MCR-1 might be traced to their cousin phosphoethanolamine (PEA) lipid A transferase from a known polymyxin producer, Paenibacillus Transcriptional analyses showed that the level of mcr-2 transcripts is relatively higher than that of mcr-1 Genetic deletions revealed that the transmembrane regions (TM1 and TM2) of both MCR-1 and MCR-2 are critical for their location and function in bacterial periplasm, and domain swapping indicated that the TM2 is more efficient than TM1. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) confirmed that all four MCR proteins (MCR-1, MCR-2, and two chimeric versions [TM1-MCR-2 and TM2-MCR-1]) can catalyze chemical modification of lipid A moiety anchored on lipopolysaccharide (LPS) with the addition of phosphoethanolamine to the phosphate group at the 4' position of the sugar. Structure-guided site-directed mutagenesis defined an essential 6-residue-requiring zinc-binding/catalytic motif for MCR-2 colistin resistance. The results further our mechanistic understanding of transferable colistin resistance, providing clues to improve clinical therapeutics targeting severe infections by MCR-2-containing pathogens.IMPORTANCE Carbapenem and colistin are the last line of refuge in fighting multidrug-resistant Gram-negative pathogens. MCR-2 is a newly emerging variant of the mobilized colistin resistance protein MCR-1, posing a potential challenge to public health. Here we report transfer of the mcr-2 gene by a unique transposal event and its possible origin. Distribution of MCR-2 in bacterial periplasm is proposed to be a prerequisite for its role in the context of biochemistry and the colistin resistance. We also define the genetic requirement of a zinc-binding/catalytic motif for MCR-2 colistin resistance. This represents a glimpse of transferable colistin resistance by MCR-2.

Project description:Klebsiella pneumoniae is a nosocomial pathogen with high morbidity and mortality rates in hospitalized patients. The emergence of multidrug-resistant K. pneumoniae has become more challenging to treat, with the prevalence of colistin-resistance. Therefore, reliable methods for detecting colistin resistance are required. Many plants' essential oils have antimicrobial activity and have been used to combat multiple antibiotic resistances. This study aimed to investigate the characterization and prevalence of the colistin resistance gene mcr-1 in K. pneumoniae in Egypt, evaluate rapid polymyxin NP test, determine the transferability of mcr-1 gene, and study the synergistic activity of eugenol combined with colistin against K. pneumoniae isolates. Eighty-two K. pneumonia isolates were collected from different human samples, followed by antibiotic susceptibility testing, rapid polymyxin NP test, and detection of the mcr-1 gene and its transfer frequency. Determination of the MICs of colistin alone and in combination with eugenol was performed, then mcr-1 gene expression was determined in the presence of eugenol. Thirty-two isolates (39%) were colistin-resistant. Rapid polymyxin NP test failed to detect resistant isolates with MICs below 32 µg/mL. Detection of mcr-1 gene was made in 27 (84%) of colistin resistant isolates. The rest isolates possess alteration in the mgrB gene which probably causes colistin resistance. The mcr-1 gene was transferred by conjugation to other sensitive isolates. MIC of eugenol ranged from 416 to 1664 µg/mL, and FICI ranged from 0.265 to 0.75. Results also revealed suppression of mcr-1 gene expression in the presence of sub MIC of eugenol. Our results demonstrated a high prevalence of mcr-1 in Egypt and its ability to transfer to other strains. Difficult determination of colistin-resistant isolates with low values with rapid polymyxin NP test was apparent. Eugenol exerted a synergistic effect with colistin and improved its antimicrobial activity.

Dataset Information

High abundance of the colistin resistance gene mcr-1 in chicken gut-bacteria in Bangladesh.

Publications

High abundance of the colistin resistance gene mcr-1 in chicken gut-bacteria in Bangladesh.

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