title: Differential host susceptibility and bacterial virulence factors driving Klebsiella liver abscess in an ethnically diverse population.
abstract: Hypervirulent Klebsiella pneumoniae is an emerging cause of community-acquired pyogenic liver abscess. First described in Asia, it is now increasingly recognized in Western countries, commonly afflicting those with Asian descent. This raises the question of genetic predisposition versus geospecific strain acquisition. We leveraged on the Antibiotics for Klebsiella Liver Abscess Syndrome Study (A-KLASS) clinical trial ongoing in ethnically diverse Singapore, to prospectively examine the profiles of 70 patients together with their isolates' genotypic and phenotypic characteristics. The majority of isolates belonged to capsule type K1, a genetically homogenous group corresponding to sequence-type 23. The remaining K2, K5, K16, K28, K57 and K63 isolates as well as two novel cps isolates were genetically heterogeneous. K1 isolates carried higher frequencies of virulence-associated genes including rmpA (regulator of mucoid phenotype A), kfu (Klebsiella ferric uptake transporter), iuc (aerobactin), iro (salmochelin) and irp (yersiniabactin) than non-K1 isolates. The Chinese in our patient cohort, mostly non-diabetic, had higher prevalence of K1 infection than the predominantly diabetic non-Chinese (Malays, Indian and Caucasian). This differential susceptibility to different capsule types among the various ethnic groups suggests patterns of transmission (e.g. environmental source, familial transmission) and/or genetic predisposition unique to each race despite being in the same geographical location.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore.
authors.forename: I Russel
authors.initials: IR
authors.lastname: Lee
authors.affiliation: Division of Infectious Diseases, University Medicine Cluster, National University Health System, Singapore.|Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore.
authors.forename: James S
authors.initials: JS
authors.lastname: Molton
authors.affiliation: Centre for Systems Genomics, University of Melbourne, Parkville, Victoria 3010, Australia.|Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Wyres
authors.affiliation: Centre for Systems Genomics, University of Melbourne, Parkville, Victoria 3010, Australia.|Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Claire
authors.initials: C
authors.lastname: Gorrie
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Wong
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore.
authors.forename: Chu Han
authors.initials: CH
authors.lastname: Hoh
authors.affiliation: Department of Laboratory Medicine, Microbiology Unit, National University Hospital, Singapore.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Teo
authors.affiliation: Department of Infectious Diseases, Singapore General Hospital, Singapore.
authors.forename: Shirin
authors.initials: S
authors.lastname: Kalimuddin
authors.affiliation: Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore.|Communicable Disease Center, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore.
authors.forename: David C
authors.initials: DC
authors.lastname: Lye
authors.affiliation: Division of Infectious Diseases, University Medicine Cluster, National University Health System, Singapore.|Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore.
authors.forename: Sophia
authors.initials: S
authors.lastname: Archuleta
authors.affiliation: Centre for Systems Genomics, University of Melbourne, Parkville, Victoria 3010, Australia.|Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Holt
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore.
authors.forename: Yunn-Hwen
authors.initials: YH
authors.lastname: Gan
mesh_terms: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins / Q000235:genetics; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007710:Klebsiella Infections / Q000235:genetics / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000235:genetics* / Q000472:pathogenicity; D008099:Liver / Q000187:drug effects* / Q000382:microbiology; D008297:Male; D010636:Phenols / Q000494:pharmacology; D012703:Serotyping; D012846:Singapore; D013844:Thiazoles / Q000494:pharmacology; D037521:Virulence Factors
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D006877:Hydroxamic Acids; D010636:Phenols; C512267:RmpA protein, Klebsiella pneumoniae; D013844:Thiazoles; D037521:Virulence Factors; C104398:yersiniabactin; C031819:aerobactin