Within-host resistance evolution of a fatal ST11 hypervirulent carbapenem-resistant Klebsiella pneumoniae

Pu, Danni; Zhao, Jun; Lu, Binghuai; Zhang, Yulin; Wu, Yongli; Li, Ziyao; Zhuo, Xianxia; Cao, Bin

doi:10.1016/j.ijantimicag.2023.106747

Cited by 31 publications

(15 citation statements)

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“…Clonal complex 258 (CC258) is one of the CRKP clones disseminating all over the world 6 . In particular, CRKP exhibiting resistance to colistin and tigecycline have raised important clinical concern, as these are the last‐line drugs for the treatment of these isolates 7 .…”

Section: Introductionmentioning

confidence: 99%

“…5 Clonal complex 258 (CC258) is one of the CRKP clones disseminating all over the world. 6 In particular, CRKP exhibiting resistance to colistin and tigecycline have raised important clinical concern, as these are the last-line drugs for the treatment of these isolates. 7 The worldwide prevalence of colistin-resistant K. pneumoniae simplified by chromosomal and plasmid-mediated LPS changes have steadily increased with increased colistin usage for treating CRKP isolates.…”

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confidence: 99%

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Molecular evaluation of aminoglycosides resistance and biofilm formation inKlebsiella pneumoniaeclinical isolates: A cross‐sectional study

Khoshnood,

Akrami,

Saki

et al. 2023

Health Science Reports

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Background and Aims Resistance to antibiotics and the capability to develop biofilm as two main virulent determinants of Klebsiella pneumoniae have important role in infection persistence. The aim of the study was to evaluate the association between the prevalence of aminoglycoside resistance and virulence genes and biofilm formation capacity in K. pneumoniae strains isolated from hospitalized patients in South‐West of Iran. Methods A total of 114 non‐duplicate clinical isolates of K. pneumoniae collected from Ahvaz teaching hospitals. Identification of species was performed by biochemical tests and then confirmed by polymerase chain reaction (PCR) of rpoB gene. The susceptibility to antibiotics was determined by Kirby−Bauer disk diffusion method. Biofilm formation was assessed by microtiter plate method. Finally, PCR was conducted to detect virulence gene determinants including fimbrial genes, aminoglycoside modifying enzymes‐ and 16S rRNA methylase (RMTase) genes. Results Totally, all collected strains were carbapenem resistant and showed multidrug‐ and extensively drug‐resistance phenotype (75% and 25%, respectively). Seventy‐one percent (n = 81) of isolates were non‐susceptible to aminoglycosides. Among aminoglycoside antibiotics, K. pneumoniae isolates showed the highest and lowest resistance rates to tobramycin (71%) and the amikacin (25%), respectively. All biofilm producer strains were positive for the presence virulence determinants including ecpA, fimA, mrkD, and mrkA. Of 81 aminoglycosides non‐susceptible isolates 33% were positive for the presence ant (2″)‐Ia as the most prevalent gene followed by aac (3′)‐IIa and armA (27%), aac (6′)‐Ib (18%), and aph (3′)‐Ia (15%). Conclusion K. pneumoniae isolates showed the highest and the lowest aminoglycoside resistance rates to tobramycin and amikacin, respectively. Majority of isolates were biofilm producers and there was significant association between antibiotic resistance pattern and the strength of biofilm production. The ant(2″)‐Ia, aac (3′)‐IIa, and armA genes in aminoglycoside‐resistant isolates.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

Molecular evaluation of aminoglycosides resistance and biofilm formation inKlebsiella pneumoniaeclinical isolates: A cross‐sectional study

Khoshnood,

Akrami,

Saki

et al. 2023

Health Science Reports

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“…The orange halos around the K. pneumoniae colonies on blue CAS agar are positive siderophore excretion. For quantitative detection, a UV–visible spectrophotometric assay was performed ( Pu et al., 2023 ). The HKE9 strain culture of 1.5 × 10 9 CFU/mL was sub-cultured into peptone liquid medium (10 g/L of peptone, 5 g/L of NaCl, pH 7.8) and incubated at 37°C for 18 h. The culture was centrifuged at 1,091 g for 15 min, and the supernatant was transferred and mixed with CAS solution for 15 min.…”

Section: Methodsmentioning

confidence: 99%

Transcriptomic and phenotype analysis revealed the role of rpoS in stress resistance and virulence of a novel ST3355 ESBL-producing hypervirulent Klebsiella pneumoniae isolate

Zhou,

Cheng,

et al. 2023

Front. Cell. Infect. Microbiol.

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IntroductionAn extended-spectrum beta-lactamase (ESBL)-hypervirulent Klebsiella pneumoniae (HvKP) strain HKE9 was isolated from the blood in an outpatient.MethodsThe effect of the global regulatory factor RpoS on antimicrobial resistance, pathogenicity, and environmental adaptability was elucidated.ResultsHKE9 is a novel ST3355 (K20/O2a) hypervirulent strain with a positive string test and resistant to cephems except cefotetan. It has a genome size of 5.6M, including two plasmids. CTX-M-15 was found in plasmid 2, and only ompk37 was found in the chromosome. HKE9 could produce bacterial siderophores, and genes of enterobactin, yersiniabactin, aerobactin, and salmochelin have been retrieved in the genome. As a global regulatory factor, knockout of rpoS did not change antimicrobial resistance or hemolytic phenotype while increasing the virulence to Galleria mellonella larvae and showing higher viscosity. Moreover, rpoS knockout can increase bacterial competitiveness and cell adhesion ability. Interestingly, HKE9-M-rpoS decreased resistance to acidic pH, high osmotic pressure, heat shock, and ultraviolet and became sensitive to disinfectants (H2O2, alcohol, and sodium hypochlorite). Although there were 13 Type 6 secretion system (T6SS) core genes divided into two segments with tle1 between segments in the chromosome, transcriptomic analysis showed that rpoS negatively regulated T4SS located on plasmid 2, type 1, and type 3 fimbriae and positively regulate genes responsible for acidic response, hyperosmotic pressure, heat shock, oxidative stress, alcohol and hypochlorous acid metabolism, and quorum sensing.DiscussionHere, this novel ST3355 ESBL-HvKP strain HKE9 may spread via various clonal types. The important regulation effect of rpoS is the enhanced tolerance and resistance to environmental stress and disinfectants, which may be at the cost of reducing virulence and regulated by T4SS.

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“…One pathway involves classic high-virulence K. pneumoniae (hvKP) acquiring plasmids or mobile elements containing carbapenem-resistant genes. Another pathway is CRKP acquiring virulence plasmids or mobile elements containing virulence genes [ 83 , 105–107 ]. It is noteworthy that through widespread transposon-mediated transposition or the fusion of resistance plasmids and virulence plasmids, virulence and resistance genes can be located on the same conjugative plasmid [ 108 , 109 ].…”

Section: Klebsiella Pneumoniaementioning

confidence: 99%

ESKAPE in China: epidemiology and characteristics of antibiotic resistance

Luo,

Lu,

Chen

et al. 2024

Emerging Microbes & Infections

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The escalation of antibiotic resistance and the diminishing antimicrobial pipeline have emerged as significant threats to public health. The ESKAPE pathogens – Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. – were initially identified as critical multidrug-resistant bacteria, demanding urgently effective therapies. Despite the introduction of various new antibiotics and antibiotic adjuvants, such as innovative β-lactamase inhibitors, these organisms continue to pose substantial therapeutic challenges. People’s Republic of China, as a country facing a severe bacterial resistance situation, has undergone a series of changes and findings in recent years in terms of the prevalence, transmission characteristics and resistance mechanisms of antibiotic resistant bacteria. The increasing levels of population mobility have not only shaped the unique characteristics of antibiotic resistance prevalence and transmission within People’s Republic of China but have also indirectly reflected global patterns of antibiotic-resistant dissemination. What’s more, as a vast nation, People’s Republic of China exhibits significant variations in the levels of antibiotic resistance and the prevalence characteristics of antibiotic resistant bacteria across different provinces and regions. In this review, we examine the current epidemiology and characteristics of this important group of bacterial pathogens, delving into relevant mechanisms of resistance to recently introduced antibiotics that impact their clinical utility in China.

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Within-host resistance evolution of a fatal ST11 hypervirulent carbapenem-resistant Klebsiella pneumoniae

Cited by 31 publications

References 49 publications

Molecular evaluation of aminoglycosides resistance and biofilm formation inKlebsiella pneumoniaeclinical isolates: A cross‐sectional study

Molecular evaluation of aminoglycosides resistance and biofilm formation inKlebsiella pneumoniaeclinical isolates: A cross‐sectional study

Transcriptomic and phenotype analysis revealed the role of rpoS in stress resistance and virulence of a novel ST3355 ESBL-producing hypervirulent Klebsiella pneumoniae isolate

ESKAPE in China: epidemiology and characteristics of antibiotic resistance

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