The Characteristic of Virulence, Biofilm and Antibiotic Resistance of Klebsiella pneumoniae

Klebsiella pneumoniae is an important gram-negative opportunistic pathogen that causes a variety of infectious diseases, including urinary tract infections, bacteremia, pneumonia, and liver abscesses. With the emergence of multidrug-resistant (MDR) and hypervirulent K. pneumoniae (hvKP) strains, the rapid spread of these clinical strains in geography is particularly worrying. However, the detailed mechanisms of virulence and antibiotic resistance in K. pneumoniae are still not very clear. Therefore, studying and elucidating the pathogenic mechanisms and drug resistance mechanism of K. pneumoniae infection are important parts of current medical research. In this paper, we systematically summarized the virulence, biofilm, and antibiotic tolerance mechanisms of K. pneumoniae, and explored the application of whole genome sequencing and global proteomics, which will provide new clues for clinical treatment of K. pneumoniae.

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Amidochelocardin Overcomes Resistance Mechanisms Exerted on Tetracyclines and Natural Chelocardin

Antibiotics ◽

10.3390/antibiotics9090619 ◽

2020 ◽

Vol 9 (9) ◽

pp. 619

Author(s):

Fabienne Hennessen ◽

Marcus Miethke ◽

Nestor Zaburannyi ◽

Maria Loose ◽

Tadeja Lukežič ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Efflux Pump ◽

Resistance Mechanism ◽

Tetracycline Resistance ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Resistance Breaking ◽

Pharmaceutical Properties ◽

Tract Infections

The reassessment of known but neglected natural compounds is a vital strategy for providing novel lead structures urgently needed to overcome antimicrobial resistance. Scaffolds with resistance-breaking properties represent the most promising candidates for a successful translation into future therapeutics. Our study focuses on chelocardin, a member of the atypical tetracyclines, and its bioengineered derivative amidochelocardin, both showing broad-spectrum antibacterial activity within the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) panel. Further lead development of chelocardins requires extensive biological and chemical profiling to achieve favorable pharmaceutical properties and efficacy. This study shows that both molecules possess resistance-breaking properties enabling the escape from most common tetracycline resistance mechanisms. Further, we show that these compounds are potent candidates for treatment of urinary tract infections due to their in vitro activity against a large panel of multidrug-resistant uropathogenic clinical isolates. In addition, the mechanism of resistance to natural chelocardin was identified as relying on efflux processes, both in the chelocardin producer Amycolatopsis sulphurea and in the pathogen Klebsiella pneumoniae. Resistance development in Klebsiella led primarily to mutations in ramR, causing increased expression of the acrAB-tolC efflux pump. Most importantly, amidochelocardin overcomes this resistance mechanism, revealing not only the improved activity profile but also superior resistance-breaking properties of this novel antibacterial compound.

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Antibiotic resistance, virulence-associated genes analysis and molecular typing of Klebsiella pneumoniae strains recovered from clinical samples

AMB Express ◽

10.1186/s13568-021-01282-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Amir Mirzaie ◽

Reza Ranjbar

Keyword(s):

Antibiotic Resistance ◽

Klebsiella Pneumoniae ◽

Molecular Typing ◽

Efflux Pump ◽

Opportunistic Pathogen ◽

Relevant Information ◽

Multidrug Resistant ◽

Clinical Samples ◽

Microbiological Methods ◽

High Level

AbstractKlebsiella pneumoniae is a multidrug-resistant (MDR) opportunistic pathogen that causes nosocomial infections. Virulence analysis and molecular typing as powerful approaches can provide relevant information on K. pneumoniae infection. In the current study, antibiotic resistance, virulence-associated genes analysis, as well as molecular typing of K. pneumoniae strains were investigated. Out of 505 clinical samples collected from hospitalized patients, 100 K. pneumoniae strains were isolated by standard microbiological methods and subjected to the phenotypic and genotyping analysis. The highest prevalence of resistance was observed against ciprofloxacin (75%), trimethoprim–sulfamethoxazole (73%) and nitrofurantoin (68%). Virulence associated genes including entB, traT, ybts, magA, iucC, htrA and rmpA were found in 80%, 62%, 75%, 5%, 30%, 72% and 48%, of the isolates, respectively. The prevalence of biofilm-associated genes including mrkA, fimH, and mrkD were equally 88% for all tested isolates. Moreover, the efflux pump genes including AcrAB, TolC and mdtK were observed in 41 (41%), 33 (33%) and 26 (26%) of the strains respectively. A significant statistical association was observed between MDR strains and high expression of efflux pump and biofilm genes. The K. pneumoniae strains were differentiated into 11 different genetic patterns using the repetitive element sequence-based PCR (rep-PCR) technique. High prevalence of resistance, presence of various virulence factors, high level of efflux pump, and biofilm gene expression in diverse clones of K. pneumoniae strains pose an important health issue in clinical settings.

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Community- and Hospital-Acquired Klebsiella pneumoniae Urinary Tract Infections in Portugal: Virulence and Antibiotic Resistance

Microorganisms ◽

10.3390/microorganisms7050138 ◽

2019 ◽

Vol 7 (5) ◽

pp. 138 ◽

Cited By ~ 17

Author(s):

Cátia Caneiras ◽

Luis Lito ◽

José Melo-Cristino ◽

Aida Duarte

Keyword(s):

Antibiotic Resistance ◽

Urinary Tract ◽

Klebsiella Pneumoniae ◽

Urinary Tract Infections ◽

Multidrug Resistant ◽

Hospital Environment ◽

Virulence Determinants ◽

Antibiotic Resistance Profile ◽

Tract Infections ◽

Hospital Acquired

Klebsiella pneumoniae is a clinically relevant pathogen and a frequent cause of hospital-acquired (HA) and community-acquired (CA) urinary tract infections (UTI). The increased resistance of this pathogen is leading to limited therapeutic options. To investigate the epidemiology, virulence, and antibiotic resistance profile of K. pneumoniae in urinary tract infections, we conducted a multicenter retrospective study for a total of 81 isolates (50 CA-UTI and 31 HA-UTI) in Portugal. The detection and characterization of resistance and virulence determinants were performed by molecular methods (PCR, PCR-based replicon typing, and multilocus sequence typing (MLST)). Out of 50 CA-UTI isolates, six (12.0%) carried β-lactamase enzymes, namely blaTEM-156 (n = 2), blaTEM-24 (n = 1), blaSHV-11 (n = 1), blaSHV-33 (n = 1), and blaCTX-M-15 (n = 1). All HA-UTI were extended-spectrum β-lactamase (ESBL) producers and had a multidrug resistant profile as compared to the CA-UTI isolates, which were mainly resistant to ciprofloxacin, levofloxacin, tigecycline, and fosfomycin. In conclusion, in contrast to community-acquired isolates, there is an overlap between virulence and multidrug resistance for hospital-acquired UTI K. pneumoniae pathogens. The study is the first to report different virulence characteristics for hospital and community K. pneumoniae pathogens, despite the production of β-lactamase and even with the presence of CTX-M-15 ESBL, a successful international ST15 clone, which were identified in both settings. This highlights that a focus on genomic surveillance should remain a priority in the hospital environment.

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Antimicrobial Resistance and Comparative Genome Analysis of Klebsiella pneumoniae Strains Isolated in Egypt

Microorganisms ◽

10.3390/microorganisms9091880 ◽

2021 ◽

Vol 9 (9) ◽

pp. 1880

Author(s):

Radwa Abdelwahab ◽

Munirah M. Alhammadi ◽

Ehsan A. Hassan ◽

Entsar H. Ahmed ◽

Nagla H. Abu-Faddan ◽

...

Keyword(s):

Antibiotic Resistance ◽

Antimicrobial Resistance ◽

Klebsiella Pneumoniae ◽

Resistance Genes ◽

Multidrug Resistant ◽

Virulence Determinants ◽

Antimicrobial Resistance Genes ◽

Tract Infections ◽

Human Infections ◽

Industrialised Countries

Klebsiella pneumoniae is an important human pathogen in both developing and industrialised countries that can causes a variety of human infections, such as pneumonia, urinary tract infections and bacteremia. Like many Gram-negative bacteria, it is becoming resistant to many frontline antibiotics, such as carbapenem and cephalosporin antibiotics. In Egypt, K. pneumoniae is increasingly recognised as an emerging pathogen, with high levels of antibiotic resistance. However, few Egyptian K. pneumoniae strains have been sequenced and characterised. Hence, here, we present the genome sequence of a multidrug resistant K. pneumoniae strain, KPE16, which was isolated from a child in Assiut, Egypt. We report that it carries multiple antimicrobial resistance genes, including a blaNDM-1 carbapenemase and extended spectrum β-lactamase genes (i.e., blaSHV-40, blaTEM-1B, blaOXA-9 and blaCTX-M-15). By comparing this strain with other Egyptian isolates, we identified common plasmids, resistance genes and virulence determinants. Our analysis suggests that some of the resistance plasmids that we have identified are circulating in K. pneumoniae strains in Egypt, and are likely a source of antibiotic resistance throughout the world.

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Antibiotic Resistance of Uropathogens Isolated from Patients Hospitalized in District Hospital in Central Poland in 2020

Antibiotics ◽

10.3390/antibiotics10040447 ◽

2021 ◽

Vol 10 (4) ◽

pp. 447

Author(s):

Barbara Kot ◽

Agata Grużewska ◽

Piotr Szweda ◽

Jolanta Wicha ◽

Urszula Parulska

Keyword(s):

Antibiotic Resistance ◽

Multidrug Resistant ◽

Diffusion Method ◽

Disk Diffusion Method ◽

Beta Lactamases ◽

E Coli ◽

Central Poland ◽

Resistance Patterns ◽

Extended Spectrum Beta Lactamases ◽

Tract Infections

The aim of this study was to determine antibiotic resistance patterns and the prevalence of uropathogenes causing urinary tract infections (UTIs) in patients hospitalized in January–June 2020 in central Poland. Antimicrobial susceptibility testing was performed using the disk-diffusion method. Escherichia coli (52.2%), Klebsiella pneumoniae (13.7%), Enterococcus faecalis (9.3%), E. faecium (6.2%), and Proteus mirabilis (4,3%) were most commonly isolated from urine samples. E. coli was significantly more frequent in women (58.6%) (p = 0.0089) and in the age group 0–18, while K. pneumoniae was more frequent in men (24.4%) (p = 0.0119) and in individuals aged 40–60 and >60. Gram-negative species showed resistance to ampicillin. K. pneumoniae were resistant to amoxicillin plus clavulanic acid (75.0%), piperacillin plus tazobactam (76.2%), cefotaxime (76.2%), cefuroxime (81.0%), ciprofloxacin (81.0%), and trimethoprim plus sulphamethoxazole (81.0%). Carbapenems were effective against all E. coli and P. mirabilis. Some K. pneumoniae (13.6%) produced metallo-β-lactamases (MBLs). E. coli (22.6%), K. pneumoniae (81.8%), and all E. faecium were multidrug-resistant (MDR). Some E. coli (26.2%), K. pneumoniae (63.6%), and P. mirabilis (14.3%) isolates produced extended-spectrum beta-lactamases (ESBL). Vancomycin-resistant E. faecium was also found. This study showed that the possibilities of UTIs therapy using available antibiotics become limited due to the increasing number of antibiotic-resistant uropathogens.

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Association of Efflux Pump and OMPs with Antibiotic Susceptibility Among ESBL-Producing Klebsiella Pneumoniae Clinical Strains in Malaysia

10.21203/rs.3.rs-375267/v1 ◽

2021 ◽

Author(s):

Golnaz Mobasseri ◽

Thong Kwai Lin ◽

Cindy Shuan Ju Teh

Keyword(s):

Antibiotic Resistance ◽

Klebsiella Pneumoniae ◽

Antibiotic Susceptibility ◽

Efflux Pump ◽

Outer Membrane Proteins ◽

Multidrug Resistant ◽

Efflux Pump Inhibitor ◽

Pump System ◽

Extended Spectrum Beta Lactamases ◽

Amoxicillin Clavulanate

Abstract Multidrug-resistant (MDR) Klebsiella pneumoniae (K. pneumoniae) poses a serious public health threat. K. pneumoniae strains that produce extended-spectrum beta-lactamases (ESBL) are becoming increasingly reported in nosocomial and community-acquired infections. Besides resistance genes, integrons, and plasmids, altered membrane permeability caused by porin loss and energy-dependent efflux have also contributed to antibiotic resistance in K. pneumoniae. The objective of this study was to determine the correlation between the reduction of antibiotic susceptibility and overexpression of efflux pump as well as the lack of outer membrane proteins (OMPs) among clinical ESBLs resistant K. pneumoniae. The expression levels of ramA, acrA, ompK35 and ompK36 in 12 MDR K. pneumoniae strains with varying MICs levels were analyzed using quantitative real time-Polymerase Chain Reaction (qRT-PCR). The role of efflux pump on antibiotic resistance was also studied by using minimum inhibitory concentration (MICs) method with//without efflux pump inhibitor. The result indicated that the strains with highest resistance to cefotaxime showed the lowest level of ompK35 and ompK36 genes expression while the strains with lowest MIC level of resistance to cefotaxime showed the highest level of expression of acrA and ramA. Our finding also revealed the effect of efflux pump inhibitor phenyl-arginine-b-naphthylamide (PAβN) on the MIC levels of ceftazidime, amoxicillin-clavulanate and cefotaxime which were significantly reduced around 1–7 folds MIC levels. These results suggest that Efflux pump system and deficiently of OMPs contributing role in antibiotic susceptibility which should be taken seriously to prevent the treatment failure due to antimicrobial resistance.

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Bacterial infections in cirrhosis: a narrative review and key points for clinical practice

Italian Journal of Medicine ◽

10.4081/itjm.2020.1306 ◽

2020 ◽

Vol 14 (3) ◽

pp. 126-135

Author(s):

Mario Mitra ◽

Andrea Mancuso ◽

Flavia Politi ◽

Alberto Maringhini

Keyword(s):

Antibiotic Resistance ◽

Bacterial Infections ◽

Empirical Therapy ◽

Multidrug Resistant ◽

High Rate ◽

First Episode ◽

Bacterial Peritonitis ◽

Prophylactic Measures ◽

Tract Infections ◽

Healthcare Associated

Bacterial infections are frequent complications of liver cirrhosis, accounting for severe clinical courses, and increased mortality. The reduction of the negative clinical impact of infections may be achieved by a combination of prophylactic measures to reduce the occurrence, early identification, and management. Spontaneous bacterial peritonitis (SBP), urinary tract infections, pneumonia, cellulitis, and spontaneous bacteremia are frequent in cirrhosis. The choice of initial empirical antimicrobial therapy should be based on both site, severity, and origin of infection (community-acquired, nosocomial, or healthcare-associated) and on antibiotic resistance patterns. 3rd generation cephalosporins are generally indicated as empirical therapy in most community-acquired cases. However, for nosocomial and healthcare-associated infections, due to a high rate of multidrug-resistant (MDR) pathogens, a broader spectrum treatment is appropriate. In order to prevent antibiotic resistance emergence, microbiological cultures should be collected, and a de-escalation applied when antimicrobial susceptibility tests are available. Standard measures to prevent infections and the identification of carriers of MDR bacteria are essential strategies to prevent infections in cirrhosis. Antibiotic prophylaxis should be applied only to gastrointestinal bleeding, SBP recurrence prevention, and cirrhotics at high risk of a first episode of SBP.

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