Gastrointestinal carriage is a major reservoir of<i>K. pneumoniae</i>infection in intensive care patients

Gorrie, Claire L.; Mirčeta, Mirjana; Wick, Ryan R.; Edwards, D.J.; Strugnell, Richard A.; Pratt, Nigel F.; Garlick, Jill; Watson, Kerrie; Pilcher, David; McGloughlin, Steven; Spelman, Denis; Jenney, Adam; Holt, Kathryn E.

doi:10.1101/096446

Cited by 31 publications

(70 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…similipneumoniae (n=20, 5.5%), K. variicola (n=9, 2.5%), and K. quasipneumoniae subsp. quasipneumoniae (n=5, 1.4%), which are not distinguishable from K. pneumoniae by standard microbiology methods 14,28 .…”

Section: Resultsmentioning

confidence: 99%

Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from south and southeast Asia

Wyres

Nguyen

Judd

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

Background: K. pneumoniae is a leading cause of blood stream infection (BSI). Strains producing extended spectrum beta--lactamases (ESBLs) or carbapenemases are considered global priority pathogens for which new treatment and prevention strategies are urgently required, due to severely limited therapeutic options. South and Southeast Asia are major hubs for antimicrobial resistant (AMR) K. pneumoniae, and also for the characteristically antimicrobial sensitive, community--acquired 'hypervirulent' strains. The emergence of hypervirulent AMR strains and lack of data on exopolysaccharide diversity pose a challenge for K. pneumoniae BSI control strategies worldwide. Methods: We conducted a retrospective genomic epidemiology study of 365 BSI K. pneumoniae from seven major healthcare facilities across South and Southeast Asia, extracting clinically relevant information (AMR, virulence, K and O antigen loci) using Kleborate. Findings: K. pneumoniae BSI isolates were highly diverse, comprising 120 multi--locus sequence types (STs) and 63 K--loci. ESBL and carbapenemase gene frequencies were 47% and 17%, respectively. The aerobactin synthesis locus (iuc), associated with hypervirulence, was detected in 28% of isolates. Importantly, 7% of isolates harboured iuc plus ESBL and/or carbapenemase genes. The latter represent genotypic AMR--virulence convergence, which is generally considered a rare phenomenon but was particularly common amongst South Asian BSI (17%). Of greatest concern, we identified seven novel plasmids carrying both iuc and AMR genes, raising the prospect of co--transfer of these phenotypes amongst K. pneumoniae. Interpretation: South and Southeast Asia are high--risk regions for the emergence of AMR and convergent AMR--hypervirulent K. pneumoniae. Enhanced surveillance efforts, reporting STs, AMR and virulence information are urgently required to monitor this public health threat. BackgroundKlebsiella pneumoniae is now regarded globally by the World Health Organisation (WHO) and others, as a priority antimicrobial resistant (AMR) pathogen requiring new control strategies 1 . These include rapid identification and containment of high--risk AMR clones such as the carbapenemase--producing (CP) variants, augmented with vaccines, bacteriophages, or immunotherapies that target conserved surface antigens. However, K. pneumoniae is highly diverse, hindering the development of such strategies and our ability to study its molecular epidemiology in a short time frame. This diverse bacterial species is generally associated with a range of differing community and healthcare--associated infections, but can be particularly problematic when the organisms gain access to sterile sites such as the cerebrospinal fluid, internal body cavities, and the bloodstream. Such infections are often characterised by rapid onset and multi--drug resistance (MDR), including resistance to third generation cephalosporins and/or carbapenems. Antimicrobials are the primary treatment strategy but options are severely limited by AMR. Concomitant w...

show abstract

Section: Resultsmentioning

confidence: 99%

Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from south and southeast Asia

Wyres

Nguyen

Judd

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…However as an opportunistic pathogen, it is likely that K. pneumoniae is more often a component of the normal animal gut microbiota. In humans the rate of intestinal K. pneumoniae colonisation has been estimated at 6% [50,51], while in dairy cows the rate may be much higher (~44% among herds in New York, USA, [52]). K. pneumoniae has also been cultured from the faeces of other agricultural and domestic animals, from the cloacae of birds, and from fish, shellfish, insects and earthworms [43,49,[53][54][55][56][57].…”

Section: Ecological Rangementioning

confidence: 99%

Klebsiella pneumoniae as a key trafficker of drug resistance genes from environmental to clinically important bacteria

Wyres

Holt

2018

Preprint

Self Cite

View full text Add to dashboard Cite

Klebsiella pneumoniae is an opportunistic bacterial pathogen known for its high frequency and diversity of antimicrobial resistance (AMR) genes. In addition to being a significant clinical problem in its own right, K. pneumoniae is the species within which several new AMR genes were first discovered before spreading to other pathogens (e.g. carbapenem--resistance genes KPC, OXA--48 and NDM--1). Whilst K. pneumoniae's contribution to the overall AMR crisis is impossible to quantify, current evidence suggests it has a wider ecological distribution, significantly more varied DNA composition, greater AMR gene diversity and a higher plasmid burden than other Gram negative opportunists. Hence we propose it plays a key role in disseminating AMR genes from environmental microbes to clinically important pathogens.

show abstract

“…Interestingly, Kp potentially exhibits diversity in metabolism and nutrient acquisition, 77 as indicated by the ability to cause a wide range of severe infections, including pneumonia, bacteremia, 78 urinary tract infection, and pyogenic liver abscess [12]. Additionally, infectious Kp frequently originates 5 79 from sites of colonization [13][14][15], including the gut and nasopharynx [16,17]; however, the impact of 80 metabolic flexibility on Kp pathogenesis has not received significant attention. 81 82 Metabolites necessary for niche invasion by pathogens can be acquired directly from the host, through 83 the metabolic activity of other microorganisms within the host microbiome, or by de novo synthesis, 84 and limitation of access to these nutrients by the host is a universal means of impeding niche invasion 85 by bacterial pathogens [18][19][20][21].…”

mentioning

confidence: 99%

TheKlebsiella pneumoniaecitrate synthase gene,gltA, influences site specific fitness during infection

Sun

Vornhagen

Breen

et al. 2019

Preprint

View full text Add to dashboard Cite

22Klebsiella pneumoniae (Kp), one of the most common causes of healthcare-associated infections, 23 increases patient morbidity, mortality and hospitalization costs. Kp must acquire nutrients from the host 24 for successful infection. However, the host is able to prevent bacterial nutrient acquisition through 25 multiple systems, including the innate immune protein lipocalin 2 (Lcn2) that prevents Kp iron 26 acquisition by sequestering the siderophore enterobactin. To identify novel Kp factors that mediate 27 evasion of nutritional immunity during lung infection, we undertook an InSeq study using a pool of 28 >20,000 transposon mutants administered to Lcn2+/+ and Lcn2-/-mice. Comparing mutant frequencies 29 between mouse genotypes, this genome-wide screen identified the Kp citrate synthase GltA as 30 potentially interacting with Lcn2, and this novel finding was independently validated. Interestingly, in 31 vitro studies suggest that this interaction is not direct. Given that GltA is involved in oxidative 32 metabolism, we screened the ability of this mutant to use a variety of carbon and nitrogen sources. The 33 results indicated that the gltA mutant has a distinct amino acid auxotrophy and is unable to use a variety 34 of carbon sources. Specifically, we show that gltA is necessary for growth in bronchioloalveolar lavage 35 fluid, which is amino acid-limited, but dispensable in serum, which is amino acid rich. Deletion of Lcn2 36 from the host leads to increased amino acid levels in bronchioloalveolar lavage fluid, and thus 37 abrogates the loss of gltA during pneumonia in the Lcn2-/-background. GltA was also required for gut 38 colonization, but dispensable in the bloodstream in a bacteremia model, demonstrating that deletion of 39 gltA leads to an organ-specific fitness defect. Together, this study is the first to mechanistically describe 40 a role for gltA in Kp infection and provide unique insight into how metabolic flexibility impacts bacterial 41 fitness during infection. 42 3 43 Author Summary 44The bacteria Klebsiella pneumoniae (Kp) is an important cause of infection in healthcare settings. 45 These infections can be difficult to treat, as they frequently occur in chronically ill patients and the 46 bacteria has the ability to acquire multiple antibiotic resistance markers. Kp is a common colonizer of 47 the intestinal tract in hospitalized patients, and can progress to infections of the bloodstream, respiratory 48 and urinary tract. However, the bacterial factors that allow Kp to replicate in these different body sites 49 is unclear. In this study, we found that the Kp citrate synthase, GltA, enables bacterial replication in the 50 lung and intestine by enhancing the ability of Kp to use diverse nutrients, in a mechanism known as 51 metabolic flexibility. Kp lacking GltA require specific amino acids that are abundant in blood, but not 52 other body sites. The work in this study provides novel insight into why Kp is a successful hospital 53 pathogen that can colonize and infect multipl...

show abstract

Gastrointestinal carriage is a major reservoir ofK. pneumoniaeinfection in intensive care patients

Cited by 31 publications

References 31 publications

Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from south and southeast Asia

Genomic surveillance for hypervirulence and multi-drug resistance in invasive Klebsiella pneumoniae from south and southeast Asia

Klebsiella pneumoniae as a key trafficker of drug resistance genes from environmental to clinically important bacteria

TheKlebsiella pneumoniaecitrate synthase gene,gltA, influences site specific fitness during infection

Contact Info

Product

Resources

About