Frequency of antiseptic resistance genes and reduced susceptibility to biocides in carbapenem-resistant Acinetobacter baumannii

Liu, Wen J.; Fu, Li; Huang, Mei‐Rong; Zhang, Jing P.; Wu, Yang; Zhou, Ying; Zeng, Jing; Wang, Guang X.

doi:10.1099/jmm.0.000403

Cited by 56 publications

(49 citation statements)

References 31 publications

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“…This, alongside the broad range of substrates (QAC compounds, disinfectants, antibiotics, etc.) that SMRs can extrude and their increasing prevalence on plasmids and integrons in clinical and multidrug-resistant strains of bacteria (13,(27)(28)(29)(30)(31)(32)(33)(34)(35), marks these proteins as important therapeutic targets.…”

Section: Discussionmentioning

confidence: 99%

Peptide-Based Efflux Pump Inhibitors of the Small Multidrug Resistance Protein from Pseudomonas aeruginosa

Mitchell

Stone

Deber

2019

Antimicrob Agents Chemother

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Bacteria have acquired multiple mechanisms to evade the lethal effects of current therapeutics, hindering treatment of bacterial infections, such as those caused by the pathogen Pseudomonas aeruginosa, which is responsible for nosocomial and cystic fibrosis lung infections. One resistance mechanism involves membrane-embedded multidrug efflux pumps that can effectively extrude an array of substrates, including common antibiotics, dyes, and biocides. Among these is a small multidrug resistance (SMR) efflux protein, consisting of four transmembrane (TM) helices, that functions as an antiparallel dimer. TM helices 1 to 3 (TM1 to TM3) comprise the substrate binding pocket, while TM4 contains a GG7 heptad sequence motif that mediates the SMR TM4-TM4 dimerization. In the present work, we synthesized a series of peptides containing the residues centered on the TM4-TM4 binding interface found in the P. aeruginosa SMR (PAsmr), typified by Ac-Ala-(Sar)3-LLGIGLIIAGVLV-KKK-NH2 (helix-helix interaction residues are underlined). Here, the acetylated N-terminal sarcosine (N-methyl-Gly) tag [Ac-Ala-(Sar)3] promotes membrane penetration, while the C-terminal Lys tag promotes selectivity for the negatively charged bacterial membranes. This peptide was observed to competitively disrupt PAsmr-mediated efflux, as measured by efflux inhibition of the fluorescent dye ethidium bromide, while having no effect on cell membrane integrity. Alternatively, a corresponding peptide in which the TM4 binding motif is scrambled was inactive in this assay. In addition, when Escherichia coli cells expressing PAsmr were combined with sublethal concentrations of several biocides, growth was significantly inhibited when peptide was added, notably, by up to 95% with the disinfectant benzylalkonium chloride. These results demonstrate promise for an efflux pump inhibitor to address the increasing threat of antibiotic-resistant bacteria.

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Section: Discussionmentioning

confidence: 99%

Peptide-Based Efflux Pump Inhibitors of the Small Multidrug Resistance Protein from Pseudomonas aeruginosa

Mitchell

Stone

Deber

2019

Antimicrob Agents Chemother

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“…A similar association occurred for over 50 isolates of carbapenem-resistant Acinetobacter baumannii. Strains obtained from four different hospitals had a high prevalence of both qac and bla genes (92).…”

Section: Cross-resistance To Antibioticsmentioning

confidence: 99%

Benzalkonium Chlorides: Uses, Regulatory Status, and Microbial Resistance

Pereira

Tagkopoulos

2019

Appl Environ Microbiol

226

153

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Benzalkonium chlorides (BACs) are chemicals with widespread applications due to their broad-spectrum antimicrobial properties against bacteria, fungi, and viruses. This review provides an overview of the market for BACs, as well as regulatory measures and available data on safety, toxicity, and environmental contamination. We focus on the effect of frequent exposure of microbial communities to BACs and the potential for cross-resistant phenotypes to emerge. Toward this goal, we review BAC concentrations in consumer products, their correlation with the emergence of tolerance in microbial populations, and the associated risk potential. Our analysis suggests that the ubiquitous and frequent use of BACs in commercial products can generate selective environments that favor microbial phenotypes potentially cross-resistant to a variety of compounds. An analysis of benefits versus risks should be the guidepost for regulatory actions regarding compounds such as BACs.

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“…[1][2][3] Especially, the New Delhi Metallo-β-lactamase (NDM), Klebsiella pneumoniae carbapenemase (KPC) and some Class D β-lactamases (CHDLs) have been identified worldwide in gram-negative bacterial isolates from clinical, environmental samples, and food animals, especially in Enterobacteriaceae, 1,[4][5][6][7][8][9] and also in Pseudomonas aeruginosa and Acinetobacter species. [10][11][12] Carbapenem-resistant Acinetobacter species are mainly associated with the carbapenem-hydrolyzing NDM and CHDLs, such as bla OXA-23 -like, bla OXA-24/40 -like, bla OXA-51 -like, bla OXA-134 -like and bla OXA-211 -like gene. [13][14][15][16][17][18] Especially, co-carrying of the bla NDM and bla OXA in clinical, food, environmental derived isolates of Acinetobacter species were prevalent in the world.…”

Section: Introductionmentioning

confidence: 99%

Whole-Genome Analysis of Two Copies of blaNDM-1 Gene Carrying Acinetobacter johnsonii Strain Acsw19 Isolated from Sichuan, China

Tang

Shen

Zhang

et al. 2020

IDR

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Purpose: To characterize the genetic feature of the carbapenems resistant Acinetobacter johnsonii strain Acsw19 isolated from municipal sludge. This strain was found to carry two copies of bla NDM-1, cmlB1-like gene, and bla OXA-211-like gene along with other 8 antimicrobial resistance genes, 3 plasmids, 15 genomic islands and 8 prophages. Methods: A carbapenem-resistant Acinetobacter johnsonii strain Acsw19 isolated from municipal sludge was subjected to whole-genome sequencing (WGS) via the PacBio and Illumina MiSeq platforms. Thereafter, the characteristic was analyzed by a series of bioinformatics software. Results: The results showed that the genome of Acsw19 was consisted of a 3,433,749 bp circular chromosome and 3 circular plasmids, pAcsw19-1 (11,161 bp), pAcsw19-2 (351,885 bp) and pAcsw19-3 (38,391bp), respectively. Resistome analysis showed that Acsw19 carried 12 antimicrobial resistance genes, including 6 [cmlB1-like, bla NDM-1 , bla OXA-58 , aph (3ʹ)-VIa, msr(E) and mph(E)] in the plasmid pAcsw19-2 and 6 (bla OXA-211-like, bla NDM-1 , aph(3")-Ib, aph(6)-Id, sul2, and floR) in the chromosome genome. Specifically, the cmlB1-like gene shared 86.33%, 71.7% and 71.9% similarities with the cmlB1, cmlA4 and cmlA8 gene, and the bla OXA-211-like gene shared 94.4%, 95.39% and 96.36% similarities with bla OXA-211 , bla OXA-643 and bla OXA-652 , at the nucleotide level, respectively. Phylogenetic analysis showed that the bla OXA-211-like gene and cmlB1-like gene had the closest evolutionary relationship with bla OXA-643 and cmlB1, respectively. These results indicated that the bla OXA-211-like and cmlB1-like genes identified in the current study should be the novel variant resistance genes. Conclusion: Carrying of two copies of bla NDM-1 , cmlB1-like, bla OXA-211-like and along with other 8 antimicrobial resistance genes, 3 plasmids, 15 genomic islands and 8 prophages Acinetobacter johnsonii strain might increase the possibility of spreading of resistance genes.

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Frequency of antiseptic resistance genes and reduced susceptibility to biocides in carbapenem-resistant Acinetobacter baumannii

Cited by 56 publications

References 31 publications

Peptide-Based Efflux Pump Inhibitors of the Small Multidrug Resistance Protein from Pseudomonas aeruginosa

Peptide-Based Efflux Pump Inhibitors of the Small Multidrug Resistance Protein from Pseudomonas aeruginosa

Benzalkonium Chlorides: Uses, Regulatory Status, and Microbial Resistance

<p>Whole-Genome Analysis of Two Copies of <em>bla</em><sub>NDM-1</sub> Gene Carrying <em>Acinetobacter johnsonii</em> Strain Acsw19 Isolated from Sichuan, China</p>

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