Genomic dissection of Klebsiella pneumoniae infections in hospital patients reveals insights into an opportunistic pathogen

Gorrie, Claire L.; Mirčeta, Mirjana; Wick, Ryan R.; Judd, Louise M.; Gomi, Ryota; Abbott, Iain J.; Thomson, Nicholas R.; Strugnell, Richard A.; Pratt, Nigel F.; Garlick, Jill; Watson, Kerrie; Hunter, Peter; Pilcher, David; McGloughlin, Steve; Spelman, Denis; Wyres, Kelly L.; Jenney, Adam; Holt, Kathryn E.

doi:10.1038/s41467-022-30717-6

Cited by 89 publications

(117 citation statements)

References 84 publications

(125 reference statements)

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“…Both sequence clusters were found in each delivery cohort. Out of these, at least ST323 has been previously associated with ESBL carriage and nosocomial transmission [22].…”

Section: Resultsmentioning

confidence: 99%

Strong pathogen competition in neonatal gut colonisation

Mäklin

Thorpe

Pöntinen

et al. 2022

Preprint

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Bacterial pathogen species and their strains that colonise the human gut are generally understood to compete against both each other and the commensal species colonising this ecosystem. However, currently we are lacking a population-wide quantification of strain-level colonisation dynamics for many common bacterial pathogens and the relationship of colonisation potential to prevalence in disease is unknown. In addition, it is unclear how ecological factors might be modulating the dynamics. Here, using a combination of latest high-resolution metagenomics and strain-level genomic epidemiology methods leveraging large genomic reference libraries of key pathogens, we performed a quantification of the competition and colonisation dynamics for a longitudinal cohort of neonatal gut microbiomes. We found a strong inter- and intra-species competition dynamic in the gut colonisation process, but also a number of synergistic relationships among several species belonging to genus Klebsiella, which includes the prominent human pathogen Klebsiella pneumoniae. Additionally, we find no evidence of preferential colonisation by hospital-adapted pathogen lineages in either vaginal or caesarean section birth groups. Our analysis also enables the first unbiased assessment of the strain-level colonisation potential of extra-intestinal pathogenic Escherichia coli (ExPEC) in comparison with their potential to cause bloodstream infections. We determined that the established common ExPEC clones ST73 and ST95 are overall significantly more pathogenic than the more recent, globally circulating multi-drug resistant clone ST131, where only a single subclone (ST131-C2) exhibited excess pathogenic potential. Our study highlights the importance of systematic surveillance of bacterial gut pathogens, not only from disease but also from carriage state, to better inform therapies and preventive medicine in the future.

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“…Both sequence clusters were found in each delivery cohort. Out of these, at least ST323 has been previously associated with ESBL carriage and nosocomial transmission [22].…”

Section: Resultsmentioning

confidence: 99%

Strong pathogen competition in neonatal gut colonisation

Mäklin

Thorpe

Pöntinen

et al. 2022

Preprint

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“…The opportunistic human and animal pathogen, causing pneumonia and urinary tract disease is Klebsiella pneumoniae (Martínez-Romero et al 2018;Rodriguez-Medina et al 2019, Gorrie et al 2022. Some strains of this bacterium cause plant diseases and some are defined as harmless or even beneficial plant endophytes (Rosenblueth et al 2004;Huang et al 2016;Duran-Bedolla et al 2021;Yang et al 2021).…”

Section: Bacterial Human Pathogens Occa-sionally Causing Plant Diseasesmentioning

confidence: 99%

Plant and Human Pathogenic Bacteria Exchanging their Primary Host Environments

Sobiczewski

Iakimova²

2022

Journal of Horticultural Research

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Adaptation of plant and human pathogenic bacteria to niches of existence differing from their original ones is a sophisticated mechanism for survival. Research indicates that certain plant bacterial pathogens are capable of causing disease in humans, and some human bacterial pathogens can inhabit the plant environment and cause disease in plants. The infection of humans by plant bacteria may occur at direct physical contact with diseased plants and/or via the respiratory tract in mainly immunocompromised or otherwise stressed individuals. Indirect transmitters of plant and human microbes can be wind, rain, dust, insects, and animals. Human pathogenic bacteria may contaminate the soil and irrigation water, colonize the rhizosphere, more rarely also the phyllosphere, and can survive as epiphytes. Thus, the plant environment may become a reservoir of human pathogens. A source of foodborne human pathogenic bacteria can be unprocessed or unwashed fruits and vegetables. Especially during the last decade, the processes underlying the cross-kingdom performance of pathogenic bacteria are intensively researched. However, in reality, the risk for human health at infections by plant bacteria and by human bacterial pathogens surviving in the plant environment is still underestimated. The goal of the current review is to increase the interest in these issues in agricultural and general environments. Some basic strategies for infection and symptoms of diseases caused by the microorganisms under consideration are described. The potency of certain plant bacterial pathogens to surpass barriers towards humans and the interaction of human bacterial pathogens with the plant environment are addressed and the existing information is critically discussed.

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“…The ICU substudy showed that the majority of K. pneumoniae infections in ICU patients (~ 80%) resulted from K. pneumoniae colonising the patients’ gut on admission to hospital, with < 20% of cases [ 14 ] resulting from nosocomial transmission. Analysis of the full collection of Alfred Health network clinical isolates reflected a similar pattern, estimating just 10% of K. pneumoniae infections resulted from nosocomial transmission [ 13 ]. Importantly ESBL carriage was the most significant risk factor for nosocomial transmission (OR 21, p < 1 × 10 −11 in a logistic regression model; estimated risk of onward transmission was 28% for ESBL strains vs 1.7% for non-ESBL strains), and transmission of ESBL strains was shown to be responsible for doubling the prevalence of ESBL + K. pneumoniae from 15% in the first 9 months of the study to > 30% in the final 3 months [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…Analysis of the full collection of Alfred Health network clinical isolates reflected a similar pattern, estimating just 10% of K. pneumoniae infections resulted from nosocomial transmission [ 13 ]. Importantly ESBL carriage was the most significant risk factor for nosocomial transmission (OR 21, p < 1 × 10 −11 in a logistic regression model; estimated risk of onward transmission was 28% for ESBL strains vs 1.7% for non-ESBL strains), and transmission of ESBL strains was shown to be responsible for doubling the prevalence of ESBL + K. pneumoniae from 15% in the first 9 months of the study to > 30% in the final 3 months [ 13 ]. The vast majority of acquired AMR genes amongst K. pneumoniae clinical infections was found to be plasmid-encoded, and the most common ESBL gene was bla CTX-M-15 ; however, plasmid transmission was not investigated.…”

Section: Introductionmentioning

confidence: 99%

“…We have previously reported WGS data from the year-long Klebsiella Acquisition Surveillance Project at Alfred Health (KASPAH), which involved the following: (i) collection of all clinical isolates identified as K. pneumoniae in the Alfred Hospital Microbiological Diagnostic Laboratory, which serves the Alfred Hospital (a large tertiary hospital with a large trauma and intensive care unit (ICU)) and three smaller hospitals (Caulfield, Bethlehem, Sandringham), together known as the Alfred Health network [ 13 ]; (ii) screening for rectal or throat colonisation with K. pneumoniae in the ICU and two geriatric wards in the Caulfield hospital [ 14 , 15 ]; (iii) screening for rectal colonisation with any 3GCR Gram negative bacteria in the ICU (substudy during the final three months) [ 16 ]. The ICU substudy showed that the majority of K. pneumoniae infections in ICU patients (~ 80%) resulted from K. pneumoniae colonising the patients’ gut on admission to hospital, with < 20% of cases [ 14 ] resulting from nosocomial transmission.…”

Section: Introductionmentioning

confidence: 99%

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ESBL plasmids in Klebsiella pneumoniae: diversity, transmission and contribution to infection burden in the hospital setting

et al. 2022

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Background Resistance to third-generation cephalosporins, often mediated by extended-spectrum beta-lactamases (ESBLs), is a considerable issue in hospital-associated infections as few drugs remain for treatment. ESBL genes are often located on large plasmids that transfer horizontally between strains and species of Enterobacteriaceae and frequently confer resistance to additional drug classes. Whilst plasmid transmission is recognised to occur in the hospital setting, the frequency and impact of plasmid transmission on infection burden, compared to ESBL + strain transmission, is not well understood. Methods We sequenced the genomes of clinical and carriage isolates of Klebsiella pneumoniae species complex from a year-long hospital surveillance study to investigate ESBL burden and plasmid transmission in an Australian hospital. Long-term persistence of a key transmitted ESBL + plasmid was investigated via sequencing of ceftriaxone-resistant isolates during 4 years of follow-up, beginning 3 years after the initial study. Results We found 25 distinct ESBL plasmids. We identified one plasmid, which we called Plasmid A, that carried blaCTX-M-15 in an IncF backbone similar to pKPN-307. Plasmid A was transmitted at least four times into different Klebsiella species/lineages and was responsible for half of all ESBL episodes during the initial 1-year study period. Three of the Plasmid A-positive strains persisted locally 3–6 years later, and Plasmid A was detected in two additional strain backgrounds. Overall Plasmid A accounted for 21% of ESBL + infections in the follow-up period. Conclusions Here, we systematically surveyed ESBL strain and plasmid transmission over 1 year in a single hospital network. Whilst ESBL plasmid transmission events were rare in this setting, they had a significant and sustained impact on the burden of ceftriaxone-resistant and multidrug-resistant infections. If onward transmission of Plasmid A-carrying strains could have been prevented, this may have reduced the number of opportunities for Plasmid A to transmit and create novel ESBL + strains, as well as reducing overall ESBL infection burden.

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Genomic dissection of Klebsiella pneumoniae infections in hospital patients reveals insights into an opportunistic pathogen

Cited by 89 publications

References 84 publications

Strong pathogen competition in neonatal gut colonisation

Strong pathogen competition in neonatal gut colonisation

Plant and Human Pathogenic Bacteria Exchanging their Primary Host Environments

ESBL plasmids in Klebsiella pneumoniae: diversity, transmission and contribution to infection burden in the hospital setting

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