<i>Klebsiella pneumoniae</i>infection biology: living to counteract host defences

Bengoechea, José A.; Sá‐Pessoa, Joana

doi:10.1093/femsre/fuy043

Cited by 384 publications

(352 citation statements)

References 267 publications

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“…The increasing challenges posed by the rise of antibiotic resistance in human pathogens have revitalized interest in the use of bacteriophage for the treatment of bacterial infections (10-12). Among MDR pathogens, CP- K. pneumoniae is a serious clinical concern, as both gut colonizer and agent of severe sepsis when invading sterile body sites (1,44). In this study, ST258 isolates were predominant in the local clinical CP- K. pneumoniae population, with overrepresentation of ST258 clade 1 (KL106-D1), reflecting the epidemiology of a recent local outbreak (9).…”

Section: Discussionmentioning

confidence: 99%

K. pneumoniaeST258 genomic variability and bacteriophage susceptibility

Venturini

Zakour

Bowring

et al. 2019

Preprint

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24Multidrug resistant carbapenemase-producing Klebsiella pneumoniae capable of causing 25 severe disease in humans is classified as an urgent threat by health agencies worldwide. 26 Bacteriophages are being actively explored as potential therapeutics against these multidrug 27 resistant pathogens. We are currently developing bacteriophage therapy against carbepenem-28 resistant K. pneumoniae belonging to the genetically diverse, globally disseminated clonal 29 group CG258. In an effort to define a robust experimental approach for effective selection of 30 lytic viruses for therapy, we have fully characterized the bacterial genomes of 18 target 31 strains, tested them against novel lytic bacteriophages, and generated phage-susceptibility 32 profiles. The genomes of K. pneumoniae isolates carrying blaNDM and blaKPC were sequenced 33 and isolates belonging to CG258 were selected for susceptibility testing using a panel of lytic 34 bacteriophages (n=65). The local K. pneumoniae CG258 population was dominated by 35 isolates belonging to sequence type ST258 clade 1 (86%). The primary differences between 36 ST258 genomes were variations in the capsular locus (cps) and in prophage content. We 37 showed that CG258-specific lytic phages primarily target the capsule, and that successful 38 infection is blocked in many, post-adsorption, by immunity conferred by existing prophages. 39Five bacteriophages specifically active against K. pneumoniae ST258 clade 1 (n=5) 40 belonging to the Caudovirales order were selected for further characterization. Our findings 41 show that effective control of K. pneumoniae CG258 with phage will require mixes of 42 diverse lytic viruses targeting all relevant cps variants and allowing for variable prophage 43 content. These insights will facilitate identification and selection of therapeutic phage 44 candidates against this serious pathogen. 45 46 47 48 Importance 49Bacteriophages are natural agents that exclusively and selectively kill bacteria and have the 50 potential to be useful in the treatment of multidrug resistant infections. K. pneumoniae 51 CG258 is a main agent of life-threatening sepsis that is often resistant to last-line antibiotics. 52Our work highlights some key requirements for developing bacteriophage preparations 53 targeting this pathogen. By defining the genomic profile of our clinical K. pneumoniae 54 CG258 population and matching it with bacteriophage susceptibility patterns, we found that 55 bacteriophage ability to lyse each strain correlates well with K. pneumoniae CG258 structural 56 subtypes (capsule variants). This indicates that preparation of bacteriophage therapeutics 57 targeting this pathogen should aim at including phages against each bacterial capsular 58 subtype. This necessitates a detailed understanding of the diversity of circulating isolates in 59 different geographical areas in order to make rational therapeutic choices. 60 61 62 Klebsiella pneumoniae is an important ubiquitous Gram-negative species capable of causing 63 disease in both humans an...

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Section: Discussionmentioning

confidence: 99%

K. pneumoniaeST258 genomic variability and bacteriophage susceptibility

Venturini

Zakour

Bowring

et al. 2019

Preprint

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“…Klebsiella pneumoniae is a clinically important pathogen, causing a wide range of diseases including pneumonia, urinary tract infections (UTIs), bloodstream infections, in hospital settings among neonates, elderly and immunocompromised individuals (Paczosa and Mecsas, 2016;Bengoechea and Sa Pessoa, 2019). Hypervirulent K. pneumoniae (hvKp) is an increasing recognized pathotype that is more virulent than classical K. pneumoniae (cKp), which showed the propensity to cause serious, lifethreatening infections in otherwise healthy individuals in the community (Shon et al, 2013;Gu et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

In vitro Activity of Apramycin Against Carbapenem-Resistant and Hypervirulent Klebsiella pneumoniae Isolates

Hao

Shi

et al. 2020

Front. Microbiol.

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Objective: The emergence of carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKp) strains poses a significant public threat, and effective antimicrobial therapy is urgently needed. Recent studies indicated that apramycin is a potent antibiotic with good activity against a range of multi-drug resistant pathogens. In this study, we evaluated the in vitro activity of apramycin against clinical CR-hvKp along with carbapenem-resistant non-hvKp (CR-non-hvKp) isolates.Methods: Broth microdilution method was used to evaluate the in vitro activities of apramycin, gentamicin, amikacin, imipenem, meropenem, doripenem, ertapenem and other comparator "last-resort" antimicrobial agents, including ceftazidime-avibactam, colistin and tigecycline, against eighty-four CR-hvKp and forty CR-non-hvKp isolates collected from three Chinese hospitals. Multilocus Sequence typing (MLST), molecular capsule typing (wzi sequencing) and antimicrobial resistance genes were examined by PCR and Sanger sequencing. Pulsed-field gel electrophoresis and next generation sequencing were conducted on selected isolates.Results: Among the 84 CR-hvKp isolates, 97.6, 100, 97.6, and 100% were resistant to imipenem, meropenem, doripenem and ertapenem, respectively. Apramycin demonstrated an MIC 50 /MIC 90 of 4/8 µg/mL against the CR-hvKp isolates. In contrast, the MIC 50 /MIC 90 for amikacin and gentamicin were >64/>64 µg/mL. All CR-hvKp isolates were susceptible to ceftazidime-avibactam, colistin and tigecycline with the MIC 50 /MIC 90 values of 0.5/1, 0.25/0.5, 1/1, respectively. For CR-non-hvKp, The MIC 50/90 values for apramycin, gentamicin and amikacin were 2/8, >64/>64, and >64/>64 µg/mL, respectively. There were no statistical significance in the resistance rates of antimicrobial agents between CR-hvKp and CR-non-hvKp groups (p > 0.05). Genetic analysis revealed that all CR-hvKp isolates harbored bla KPC-2 , and 94% (n = 79) belong to the ST11 high-risk clone. 93.6% (44/47) of amikacin or gentamicin resistant strains carried 16S rRNA methyltransferases gene rmtB.

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“…Klebsiella pneumoniae (KP) is a ubiquitous species in nature, a gut commensal, and a human opportunistic pathogen. It can cause a wide range of infections, including pneumonia, urinary tract infections, bacteremia and liver abscesses [17,18]. Due to the frequent occurrence of multiple antibiotic-resistant isolates, K. pneumoniae is considered a global public health concern [19-21] .…”

Section: Introductionmentioning

confidence: 99%

Insights into Klebsiella pneumoniae type VI secretion system transcriptional regulation

Barbosa

Lery

2019

BMC Genomics

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Background Klebsiella pneumoniae (KP) is an opportunistic pathogen that mainly causes respiratory and urinary tract infections. The frequent occurrence of simultaneously virulent and multiple drug-resistant isolates led WHO to include this species in the list of top priorities for research and development of therapeutic alternatives. The comprehensive knowledge of the molecular mechanisms underlying KP virulence may lead to the proposal of more efficient and specific drugs. One of its virulence factors is the Type VI Secretion System (T6SS), which contributes to bacterial competition, cell invasion and in vivo colonisation. Despite the few studies showing the involvement of T6SS in KP pathogenesis, little is known concerning the regulation of its expression. The understanding of regulatory mechanisms may give more clues about the function of the system and the possibilities of future interference in this process. This work aimed to standardise the annotation of T6SS genes in KP strains and identify mechanisms of their transcriptional regulation through computational predictions. Results We analyzed the genomes of Kp52.145, HS11286 and NTUH-K2044 strains to perform a broad prediction and re-annotation of T6SS genes through similarity searches, comparative and linear discriminant analysis. 38 genes were found in Kp52.145, while 29 in HS11286 and 30 in NTUH-K2044. Genes coding for iron uptake systems are encoded in adjacencies of T6SS, suggesting that KP T6SS might also play a role in ion import. Some of the T6SS genes are comprised in syntenic regions. 17 sigma 70-dependent promoter regions were identified in Kp52.145, 12 in HS11286 and 12 in NTUH-K2044. Using VirtualFootprint algorithm, binding sites for 13 transcriptional regulators were found in Kp52.145 and 9 in HS11286 and 17 in NTUH-K2044. Six of them are common to the 3 strains: OxyR, H-NS, RcsAB, GcvA, Fis, and OmpR. Conclusions The data presented herein are derived from computational analysis. Although future experimental studies are required to confirm those predictions, they suggest that KP T6SS might be regulated in response to environmental signals that are indeed sensed by the bacteria inside the human host: temperature (H-NS), nutrition-limitation (GcvA and Fis), oxidative stress (OxyR) and osmolarity (RscAB and OmpR). Electronic supplementary material The online version of this article (10.1186/s12864-019-5885-9) contains supplementary material, which is available to authorized users.

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Klebsiella pneumoniaeinfection biology: living to counteract host defences

Cited by 384 publications

References 267 publications

K. pneumoniaeST258 genomic variability and bacteriophage susceptibility

K. pneumoniaeST258 genomic variability and bacteriophage susceptibility

In vitro Activity of Apramycin Against Carbapenem-Resistant and Hypervirulent Klebsiella pneumoniae Isolates

Insights into Klebsiella pneumoniae type VI secretion system transcriptional regulation

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