Resistance elicited by sub-lethal concentrations of ampicillin is partially mediated by quorum sensing in Pseudomonas aeruginosa

Li, Yue; Xia, Lei; Chen, Jian; Lian, Yulu; Dandekar, Ajai A.; Xu, Feng; Wang, Meizhen

doi:10.1016/j.envint.2021.106619

Cited by 24 publications

(25 citation statements)

References 43 publications

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“…ZapE is a conditional cell division protein, but its role in conferring antibiotic resistance has not been reported. Mutations in mpl were frequently detected, displaying strong correlations with antibiotic resistance against ampicillin, ciprofloxacin, etc . Nevertheless, its detailed antibiotic resistance mechanism is not yet known.…”

Section: Resultsmentioning

confidence: 99%

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Low-Level Cefepime Exposure Induces High-Level Resistance in Environmental Bacteria: Molecular Mechanism and Evolutionary Dynamics

Wang

Feng

Lü

2022

Environ. Sci. Technol.

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Antibiotics exert selective pressures on clinically relevant antibiotic resistance. It is critical to understand how antibiotic resistance evolves in environmental microbes exposed to subinhibitory concentrations of antibiotics and whether evolutionary dynamics and emergence of resistance are predictable. In this study, Comamonas testosteroni isolated from wastewater activated sludge were subcultured in a medium containing 10 ng/mL cefepime for 40 days (∼300 generations). Stepwise mutations were accumulated, leading to an ultimate 200-fold increase in the minimum inhibitory concentration (MIC) of cefepime. Early stage mutation in DNA polymerase-encoding gene dnaE2 played an important role in antibiotic resistance evolution. Diverse resistance mechanisms were employed and validated experimentally, including increased efflux, biofilm formation, reduced antibiotic uptake, and drug inactivation. The cefepime minimal selective concentrations (MSCs) and relative fitness of susceptible, intermediate, and resistant mutants were determined. Agent-based modeling of the modified Moran process enabled simulations of resistance evolution and predictions of the emergence time and frequency of resistant mutants. The unraveled cefepime resistance mechanisms could be employed by broader bacteria, and the newly developed model is applicable to the predictions of general resistance evolution. The improved knowledge facilitates the assessment, prediction, and mitigation of antibiotic resistance progression in antibiotic-polluted environments.

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Section: Resultsmentioning

confidence: 99%

“…Mutations in mpl were frequently detected, displaying strong correlations with antibiotic resistance against ampicillin, ciprofloxacin, etc. 43 Nevertheless, its detailed antibiotic resistance mechanism is not yet known. ]…”

Section: Evolutionary Trajectory and Mechanism Of Cefepime Resistancementioning

confidence: 99%

Low-Level Cefepime Exposure Induces High-Level Resistance in Environmental Bacteria: Molecular Mechanism and Evolutionary Dynamics

Wang

Feng

Lü

2022

Environ. Sci. Technol.

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“…Thus, the enhancement of β-lactamase production is the evident explanation for the expression of phenotypic resistance in the mutant isolates. Although Mpl in Enterobacterales has received little attention, studies have shown that mutations in mpl can activate β-lactamase production in S. maltophilia and P. aeruginosa [18][19][20][21]. Calvopina and colleagues showed that clinical isolates of S. maltophilia with mutations in mpl expressed β-lactamase hyperproduction, as evaluated by nitrocefin hydrolysis [18].…”

Section: Discussionmentioning

confidence: 99%

“…Calvopina and colleagues showed that clinical isolates of S. maltophilia with mutations in mpl expressed β-lactamase hyperproduction, as evaluated by nitrocefin hydrolysis [18]. Li and colleagues challenged P. aeruginosa with sub-lethal concentrations of ampicillin, mpl was frequently mutated in sequenced strains, and transcriptome analysis revealed a 7-9-fold upregulation of ampC [21]. In the present study, we also tested other βlactam antimicrobials by plating on LB-agar containing 50 µg/mL piperacillin or ampicillin.…”

Section: Discussionmentioning

confidence: 99%

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Induction of Broad β-lactam Resistance in Achromobacter ruhlandii by Exposure to Ticarcillin Is Primarily Linked to Substitutions in Murein Peptide Ligase Mpl

2022

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Achromobacter species are emerging pathogens in cystic fibrosis with inherent resistance to several classes of antimicrobial agents. We exposed strains with wild-type antimicrobial susceptibility to ticarcillin and generated mutants with broad β-lactam resistance. Within the detection limit of the assay, the capability to develop mutational resistance was strain-specific and reproducible. Mutational resistance was observed for all three tested strains of Achromobacter ruhlandii, for one of seven strains of Achromobacter xylosoxidans, and for none of five strains of Achromobacter insuavis. All mutants were resistant to piperacillin-tazobactam, while minimal inhibitory concentration of several other β-lactams increased 4–32-fold. Whole genome sequencing identified 1–4 non-synonymous mutations in known genes per mutant. All mutants encoded amino acid substitutions in cell wall recycling proteins, primarily Mpl, and the observed resistance is probably caused by hyperproduction of OXA-114-like β-lactamases. Related, but not identical substitutions were detected in clinical strains expressing acquired antimicrobial resistance.

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Genome editing in Acinetobacter baumannii through enhanced natural transformation

Yilmaz,

Ozbek

2024

J Basic Microbiol

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Acinetobacter baumannii, a multidrug‐resistant bacterium has become a significant cause of life‐threatening infections acquired in hospitals worldwide. The existing drugs used to treat A. baumannii infections are rapidly losing efficacy, and the increasing antimicrobial resistance, which is expected to turn into a global health crisis, underscores the urgency to develop novel prevention and treatment strategies. We reasoned that the discovery of novel virulence targets for vaccine and therapy interventions requires a more enhanced method for the introduction of multiple elements of foreign DNA for genome editing than the current methods of natural transformation techniques. Herein, we employed a novel and a much‐improved enhanced technique for the natural transformation of elements of the genome editing system CRISPR‐Cas9 to suppress specific genomic regions linked to selectively suppress bacterial virulence. We modified the genome of the laboratory‐adapted strain of A. baumannii BAA‐747 by targeting the AmpC, as a marker gene, for disruption by three different genomic manipulation strategies, and created mutant strains of A. baumannii that are, at least, fourfold susceptible to ampicillin. This work has established an optimized enhanced natural transformation system that enables efficient genome editing of pathogenic bacteria in a laboratory setting, providing a valuable future tool for exploring the function of unidentified virulence genes in bacterial genomes.

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Resistance elicited by sub-lethal concentrations of ampicillin is partially mediated by quorum sensing in Pseudomonas aeruginosa

Cited by 24 publications

References 43 publications

Low-Level Cefepime Exposure Induces High-Level Resistance in Environmental Bacteria: Molecular Mechanism and Evolutionary Dynamics

Low-Level Cefepime Exposure Induces High-Level Resistance in Environmental Bacteria: Molecular Mechanism and Evolutionary Dynamics

Induction of Broad β-lactam Resistance in Achromobacter ruhlandii by Exposure to Ticarcillin Is Primarily Linked to Substitutions in Murein Peptide Ligase Mpl

Genome editing in Acinetobacter baumannii through enhanced natural transformation

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