Proteomic Profiling of
            <i>Klebsiella Pneumoniae</i>
            Carbapenemase (KPC)-Producer
            <i>Klebsiella Pneumoniae</i>
            After Induced Polymyxin Resistance

Queiroz, Paula Assis; Meneguello, Jean Eduardo; Silva, Bruna R; Caleffi-Ferracioli, Katiany Rizzieri; Scodro, Regiane Bertin de Lima; Cardoso, Rosilene Fressatti; Marchiosi, Rogério; Siqueira, Vera Ld

doi:10.2217/fmb-2021-0005

Cited by 3 publications

(1 citation statement)

References 50 publications

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“…Other enriched mutations potentially affecting outer barrier of the cell were between the genes slyB (-3) and anmK (-271) in Ag3_LD, between yegH (-47) and wza (-612) in Ag5_LD and rfaJ S245C in Cu3_HH. SlyB is a stress-induced PhoPQ-regulated outer membrane lipoprotein that is essential in outer membrane stabilization [92] and is associated with antimicrobial peptide and polymyxin B tolerance [93], [94], [95] while AnmK participates in peptidoglycan recycling [96]. YegH encodes a putative inner membrane transporter immediately neighboring the colonic acid transport and synthesis genes starting with wza in the opposite direction [97].…”

Section: Mutations: Cell Surface and Membrane Transportmentioning

confidence: 99%

Experimental evolution ofEscherichia colion solid silver, copper, stainless steel, and glass surfaces

Rosenberg,

Park,

Umerov

et al. 2024

Preprint

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To study bacterial adaptation to antimicrobial metal surfaces in application-relevant semi-dry environmental conditions,Escherichia coliATCC 8739 was exposed to copper, silver, stainless steel, and glass surfaces for thirty consecutive cycles in exposure conditions designed to select for either survival or growth. Subsequent mutation analysis did not find changes in overall mutation frequency that could lead to enhanced adaptation potential nor mutations incop, cus, cue, sil, pcoor general efflux genes known to actively maintain copper/silver homeostasis in copper or silver exposed populations compared to populations evolved on steel and glass control surfaces. However, mutations insilSrapidly activated the crypticsilefflux locus during silver ion challenge in liquid assay with the evolved populations and caused collateral increase in ampicillin and ciprofloxacin tolerance, indicating that efflux might be specific to granting heavy metal tolerance in liquid but not surface exposure format. Instead, during cyclic surface exposure mutations in genes related to cellular barrier functions and sulfur metabolism were enriched on copper and silver surfaces. This increased metal surface tolerance but had less to no protective effect in subsequent conventional MBC and MIC tests indicating that reducing bioavailability and passively restricting uptake of the toxic metals rather than active efflux contributes to increased viability on copper and silver surfaces compared to liquid format. Our findings highlight the critical importance of appropriate exposure conditions not only in efficacy assessment but also risk assessment of antimicrobial surfaces rendering results acquired via liquid tests not applicable for dry-use surfaces.ImportanceThis study examines the evolutionary adaptations ofEscherichia coliunder sublethal exposure to copper and silver surfaces, revealing a moderate increase in surface tolerance but no heightened mutation frequency or enhanced metal ion tolerance in standard tests. Notably, enriched mutations indicate a shift toward more energy-passive mechanisms of metal tolerance. Additionally, while enhanced silver efflux—with a collateral increase in antibiotic tolerance—was rapidly selected in a single round of silver exposure in liquid tests and substantially increased copper and silver ion tolerance in conventional test formats, the causal mutations did not improve viability on silver and copper surfaces, underscoring the different fitness dynamics of tolerance mechanisms dependent on exposure conditions. These findings emphasize the need for appropriate exposure conditions in evaluating of both efficacy and the potential risks of using antimicrobial surfaces, as the results from conventional liquid-based tests may not apply in solid contexts.

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Section: Mutations: Cell Surface and Membrane Transportmentioning

confidence: 99%

Experimental evolution ofEscherichia colion solid silver, copper, stainless steel, and glass surfaces

Rosenberg,

Park,

Umerov

et al. 2024

Preprint

View full text Add to dashboard Cite

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Outbreak by KPC-62-producing ST307 Klebsiella pneumoniae isolates resistant to ceftazidime/avibactam and cefiderocol in a university hospital in Madrid, Spain

Castillo-Polo

Hernández-García

Morosini

et al. 2023

Journal of Antimicrobial Chemotherapy

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Objectives Ceftazidime/avibactam and cefiderocol are two of the latest antibiotics with activity against a wide variety of Gram-negatives, including carbapenem-resistant Enterobacterales. We sought to describe the phenotypic and genotypic characteristics of ceftazidime/avibactam- and cefiderocol-resistant KPC-Klebsiella pneumoniae (KPC-Kp) detected during an outbreak in 2020 in the medical ICU of our hospital. Methods We collected 11 KPC-Kp isolates (6 clinical; 5 surveillance samples) resistant to ceftazidime/avibactam and cefiderocol from four ICU patients (November 2020 to January 2021), without prior exposure to these agents. All patients had a decontamination regimen as part of the standard ICU infection prevention protocol. Additionally, one ceftazidime/avibactam- and cefiderocol-resistant KPC-Kp (June 2019) was retrospectively recovered. Antibiotic susceptibility was determined by broth microdilution. β-Lactamases were characterized and confirmed. WGS was also performed. Results All KPC-Kp isolates (ceftazidime/avibactam MIC ≥16/4 mg/L; cefiderocol MIC ≥4 mg/L) were KPC + CTX-M-15 producers and belonged to the ST307 high-risk-clone (ST307-HRC). KPC-62 (L168Q) was detected in all isolates involved in the 2020 outbreak, contained in January 2021. KPC-31 (D179Y) was identified in the KPC-Kp from 2019. Cloning experiments demonstrated that both blaKPC-62 and blaKPC-31 were responsible for ceftazidime/avibactam resistance (MIC >16 mg/L) and an increased cefiderocol MIC. Additionally, mutations in OmpA and EnvZ/OmpR porin proteins (in KPC-62-Kp) and in PBP2 (in KPC-31-Kp) were found and may be involved in cefiderocol resistance. Conclusions The emergence of resistance to both ceftazidime/avibactam and cefiderocol in KPC-Kp-HRCs, together with the diversification of novel KPC enzymes displaying different antibiotic resistance phenotypes, is an epidemiological and clinical risk.

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Clinical analysis of colistin sulfate in the treatment of pneumonia caused by carbapenem-resistant Gram-negative bacteria

Xu,

Cui,

Wang

et al. 2024

World J Clin Cases

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BACKGROUND Multidrug-resistant Gram-negative bacteria, exacerbated by excessive use of antimicrobials and immunosuppressants, are a major health threat. AIM To study the clinical efficacy and safety of colistin sulfate in the treatment of carbapenem-resistant Gram-negative bacilli-induced pneumonia, and to provide theoretical reference for clinical diagnosis and treatment. METHODS This retrospective analysis involved 54 patients with Gram-negative bacilli pneumonia admitted to intensive care unit of The General Hospital of the Northern Theater Command of the People's Liberation Army of China from August 2020 to June 2022. After bacteriological culture, the patients' airway secretions were collected to confirm the presence of Gram-negative bacilli. The patients were divided into the experimental and control groups according to the medication used. The research group consisted of 28 patients who received polymyxin sulfate combined with other drugs through intravenous, nebulization, or intravenous combined with nebulization, with a daily dosage of 1.5–3.0 million units. The control group consisted of 26 patients who received standard dosages of other antibiotics (including sulbactam sodium for injection, cefoperazone sodium sulbactam for injection, tigecycline, meropenem, or vaborbactam). RESULTS Of the 28 patients included in the research group, 26 patients showed improvement, treatment was ineffective for two patients, and one patient died, with the treatment efficacy rate of 92.82%. Of the 26 patients in the control group, 18 patients improved, treatment was ineffective for eight patients, and two patients died, with the treatment efficacy rate of 54.9%; significant difference was observed between the two groups (P < 0.05). The levels of white blood cell (WBC), procalcitonin (PCT), and C-reactive protein (CRP) in both groups were significantly lower after treatment than before treatment (P < 0.05), and the levels of WBC, PCT, and CRP in the research group were significantly lower than those in the control group (P < 0.05). Compared with before treatment, there were no significant changes in aspartate aminotransferase, creatinine, and glomerular filtration rate in both groups, while total bilirubin and alanine aminotransferase decreased after treatment (P < 0.05) with no difference between the groups. In patients with good clinical outcomes, the sequential organ failure assessment (SOFA) score was low when treated with inhaled polymyxin sulfate, and specific antibiotic treatment did not improve the outcome. Sepsis and septic shock as well as a low SOFA score were independent factors associated with good clinical outcomes. CONCLUSION Polymyxin sulfate has a significant effect on the treatment of patients with multiple drug-resistant Gram-negative bacilli pneumonia and other infections in the lungs and is safe and reliable. Moreover, the administration route of low-dose intravenous injection combined with nebulization shows better therapeutic effects and lower adverse reactions, providing new ideas for clinical administration.

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Proteomic Profiling of Klebsiella Pneumoniae Carbapenemase (KPC)-Producer Klebsiella Pneumoniae After Induced Polymyxin Resistance

Cited by 3 publications

References 50 publications

Experimental evolution ofEscherichia colion solid silver, copper, stainless steel, and glass surfaces

Experimental evolution ofEscherichia colion solid silver, copper, stainless steel, and glass surfaces

Outbreak by KPC-62-producing ST307 Klebsiella pneumoniae isolates resistant to ceftazidime/avibactam and cefiderocol in a university hospital in Madrid, Spain

Clinical analysis of colistin sulfate in the treatment of pneumonia caused by carbapenem-resistant Gram-negative bacteria

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