Porin loss in Klebsiella pneumoniae clinical isolates impacts production of virulence factors and survival within macrophages

Brunson, Debra N; Maldosevic, Emir; Velez, Amanda; Figgins, Erika; Ellis, Terri N.

doi:10.1016/j.ijmm.2019.04.001

Cited by 15 publications

(10 citation statements)

References 43 publications

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“…44,45 The reasons for antimicrobial drug resistance in Klebsiella pneumoniae could be due to diminished expression/loss of porin channels, alteration in outer membrane proteins (OMP) permeability, or efflux pump overexpression & carbapenem hydrolysis. 46 KPCs also inactivate all beta-lactam antibiotics and are only partially inhibited by beta-lactamase inhibitors like clavulanic acid, tazobactam and boronic acid. 47…”

Section: Discussionmentioning

confidence: 99%

Phenotypic Characterization of Virulence Factors and Antibiogram of Klebsiella pneumoniae Isolates from Various Clinical Samples – A Cross Sectional Study

Hullur¹,

Natarajan²,

Sreeramulu³

2022

J. Pure Appl. Microbiol.

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K. pneumoniae is known to cause hospital and community acquired infections. It is usually associated with upper & lower respiratory infections, septicaemia, urinary tract infection, wound infections, neonatal sepsis, meningitis, and endophthalmitis. The virulence factors play a role in its existence in different environmental conditions and therefore help in establishing Klebsiella pneumoniae infection in the human body. Multi drug resistant Klebsiella pneumoniae is an increasing threat to human health. Klebsiella pneumoniae is one of the species recognized as nosocomial pathogens that exhibit multidrug resistance and virulence in ESKAPE group as per WHO. The study was conducted to determine the various virulence factors & the antimicrobial pattern of Klebsiella pneumoniae isolates. A cross sectional observational study, conducted in Department of Microbiology of R.L. Jalappa Hospital and Research Centre, Kolar, Sample size of 150. All 150 Klebsiella pneumoniae isolates collected for the study, The Klebsiella pneumoniae isolates which were positive for various virulence factors were as follows on hemolysis 7(4.66%), capsule 150(100%), Hypermucoviscosity formation 66(44%), biofilm production 81(54%), siderophore production 110(73.33%), protease 135(90%), gelatinase 126(84%), lipase production 119(79.33%), lecithinase activity 82(54.66%). The drug resistance klebsiella pneumoniae were as follows: ESBL producers 24(16.67%), AmpC producers were 22(14.67%), MDR 116(74.20%), extensive drug resistant (XDR) 30(20%), pan drug resistant (PDR) 42(28%), Carbapenem resistance 65.33% reported. The increasing coexistence of virulence factors & antimicrobial resistance pattern is of particular concern. Hence active surveillance for antimicrobial resistance & virulence determinants is imperative now to implement effective control measures to prevent the rapid spread of drug resistance.

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Section: Discussionmentioning

confidence: 99%

Phenotypic Characterization of Virulence Factors and Antibiogram of Klebsiella pneumoniae Isolates from Various Clinical Samples – A Cross Sectional Study

Hullur¹,

Natarajan²,

Sreeramulu³

2022

J. Pure Appl. Microbiol.

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“…However, given that porin loss is a very common feature in patients' isolates (Nordmann and Poirel, 2019), a reduction in growth yield seems to be an acceptable trade-off, at least in clinical settings, where constant antibiotic challenges, even at low concentrations, select for antibiotic resistant strains (Gullberg et al, 2011). Furthermore, for Klebsiella pneumoniae it was recently demonstrated that porin loss promotes increased survival within macrophages, indicating certain fitness advantages for porin-mutant strains in the host (Brunson et al, 2019), even without antibiotic pressure.…”

Section: Discussionmentioning

confidence: 99%

The Resistance Mechanism Governs Physiological Adaptation of Escherichia coli to Growth With Sublethal Concentrations of Carbapenem

et al. 2022

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Factors governing resistance in carbapenem-resistant Enterobacteriaceae are manifold. Despite ample research efforts, underlying molecular mechanisms are still only partly understood. Furthermore, little is known on (eco)physiological consequences from resistance acquisition originating from distinct mechanisms in respective bacteria.In this study, we examined physiological adaptation of Escherichia coli clinical isolates exhibiting two distinct resistance mechanisms–either carrying a carbapenemase (n = 4, CARB) or alterations in porin-encoding genes (n = 6, POR)–during growth with sublethal concentrations of ertapenem in chemostat culture. Basic growth parameters based on optical density and flow-cytometric analyses as well as global gene expression patterns using RNA-Seq were recorded. We demonstrate that strategies to deal with the antibiotic were distinct between strains of the two groups, where (increased) expression of carbapenemases was the major response in CARB, whereas wide-spread alterations in gene-expression that promoted a survival-like phenotype was observed in POR. The response in POR was accompanied with “costs of resistance” resulting in reduced growth efficiencies compared with CARB that are intrinsic to that group and were also observed during growth without antibiotic challenge, however, at lower levels. All strains showed similar minimal inhibitory concentrations and did not form phylogenetic groups, indicating that results cannot be attributed to distinct resistance levels or phylogenetic relationships, but are indeed based on the resistance mechanism.

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“…The carbohydrate composition of the CPS was characterized by GC-MS as previously detailed in Brunson et al (20). Briefly, CPS was purified from LPS using sodium deoxycholate at a final concentration of 6 mM as described by Kachlany et al (21).…”

Section: Methodsmentioning

confidence: 99%

Progressive sub-MIC Exposure ofKlebsiella pneumoniae43816 to Cephalothin Induces the Evolution of beta-lactam Resistance without Acquisition of beta-lactamase Genes

Anderson

Lam

Jackson

et al. 2021

Preprint

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Bacterial exposure to antibiotic concentrations below the minimum inhibitory concentration (MIC) may result in a selection window allowing for the rapid evolution of resistance. These sub-MIC concentrations are commonly found in the greater environment. This study aimed to evaluate the adaptive genetic changes in Klebsiella pneumoniae 43816 after prolonged but increasing sub-MIC levels of the common antibiotic cephalothin over a fourteen-day period. Over the course of the experiment, antibiotic concentrations increased from 0.5 μg/mL to 7.5 μg/mL. At the end of this extended exposure, the final adapted bacterial culture exhibited clinical resistance to both cephalothin and tetracycline, altered cellular and colony morphology, and a highly mucoid phenotype. Cephalothin resistance exceeded 125 μg/mL without the acquisition of beta-lactamase genes. Whole genome sequencing identified a series of genetic changes that could be mapped over the fourteen-day exposure period to the onset of antibiotic resistance. Specifically, mutations in the rpoB subunit of RNA Polymerase, the tetR/acrR regulator, and the wcaJ sugar transferase each fix at specific timepoints in the exposure regimen where the MIC susceptibility dramatically increases. These mutations indicate that alterations in the secretion of colanic acid and attachment of colonic acid to LPS, may contribute to the resistant phenotype. These data demonstrate that very low, sub-MIC concentrations of antibiotics can have dramatic impacts on the bacterial evolution of resistance. Additionally, this study demonstrates that beta-lactam resistance can be achieved through sequential accumulation of specific mutations without the acquisition of a beta-lactamase gene.ImportanceBacteria are constantly exposed to low levels of antibiotics in the environment. The impact of this low-level exposure on bacterial evolution is not well understood. In this work, we developed a model to expose Klebsiella pneumoniae to progressive, low doses of the antibiotic cephalothin. After a fourteen-day exposure regimen, our culture exhibited full clinical resistance to this antibiotic without the traditional acquisition of inactivating genes. This culture also exhibited resistance to tetracycline, had a highly mucoid appearance, and exhibited altered, elongated cellular morphology. Whole genome sequencing identified a collection of mutations to the bacterial genome that could be mapped to the emergence of the resistant phenotype. This study demonstrates that antibiotic resistance can be achieved in response to low level antibiotic exposure and without the traditional acquisition of resistance genes. Further, this study identifies new genes that may play a role in the evolution of antibiotic resistant bacteria.

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Porin loss in Klebsiella pneumoniae clinical isolates impacts production of virulence factors and survival within macrophages

Cited by 15 publications

References 43 publications

Phenotypic Characterization of Virulence Factors and Antibiogram of Klebsiella pneumoniae Isolates from Various Clinical Samples – A Cross Sectional Study

Phenotypic Characterization of Virulence Factors and Antibiogram of Klebsiella pneumoniae Isolates from Various Clinical Samples – A Cross Sectional Study

The Resistance Mechanism Governs Physiological Adaptation of Escherichia coli to Growth With Sublethal Concentrations of Carbapenem

Progressive sub-MIC Exposure ofKlebsiella pneumoniae43816 to Cephalothin Induces the Evolution of beta-lactam Resistance without Acquisition of beta-lactamase Genes

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