Characterization of Pre-Antibiotic Era Klebsiella pneumoniae Isolates with Respect to Antibiotic/Disinfectant Susceptibility and Virulence in Galleria mellonella

Wand, Matthew E.; Baker, Kate S.; Benthall, Gabriel; McGregor, Hannah; McCowen, James W. I.; Deheer-Graham, Ana; Sutton, J. Mark

doi:10.1128/aac.05009-14

Cited by 59 publications

(49 citation statements)

References 44 publications

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“…The available data suggest that no particular virulence factor of CG23 is necessary or sufficient for invasive disease. Three liver abscess strains lacked ICEKp, and it was recently reported that the 1932 Murray Collection isolate lacking ICEKp is highly virulent in the Galleria mellonella infection model 37 . Both asymptomatic carriage isolates in our study lacked ICEKp, however the significance of this is not yet clear.…”

Section: Discussionmentioning

confidence: 99%

“…We identified 83 CG23 genome sequences from our curated collection (six finished and 77 draft genomes, see Table S1 26,38 ). These included 43 genomes from our own previous studies 19,21,27,69 and 40 publicly available genomes including the 27 analysed by Struve et al 28,29,37,68,[70][71][72][73][74] . We also sequenced 15 novel genomes that were identified as ST23 by MLST (02A029, 12A041 and 16A151 14 ) or identified as K1 by classical serotyping and then confirmed as ST23 by genome sequencing (12 strains isolated between 1980 and 1987 from samples from horses; see Table S1).…”

Section: Genome Collectionmentioning

confidence: 99%

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Population genomics of hypervirulentKlebsiella pneumoniaeclonal group 23 reveals early emergence and rapid global dissemination

Wyres

Duchêne

Wick

et al. 2017

Preprint

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Since the mid-1980s there have been increasing reports of severe community-acquired pyogenic liver abscess, meningitis and bloodstream infections caused by hypervirulent Klebsiella pneumoniae, predominantly encompassing clonal group (CG) 23 serotype K1 strains. Common features of CG23 include a virulence plasmid associated with iron scavenging and hypermucoidy, and a chromosomal integrative and conjugative element (ICE) encoding the siderophore yersiniabactin and the genotoxin colibactin. Here we investigate the evolutionary history and genomic diversity of CG23 based on comparative analysis of 98 genomes. Contrary to previous reports with more limited samples, we show that CG23 comprises several deep branching sublineages dating back to the 1870s, many of which are associated with distinct chromosomal insertions of ICEs encoding yersiniabactin. We find that most liver abscess isolates (>80%) belong to a dominant sublineage, CG23-I, which emerged in the 1920s following acquisition of ICEKp10 (encoding colibactin in addition to yersiniabactin) and has undergone clonal expansion and global dissemination within the human population. The unique genomic feature of CG23-I is the production of colibactin, which has been reported previously as a promoter of gut colonisation and dissemination to the liver and brain in a mouse model of CG23 K. pneumoniae infection, and has been linked to colorectal cancer. We also identify an antibiotic-resistant subclade of CG23-I associated with sexually-transmitted infections in horses dating back to the 1980s. These data show that hypervirulent CG23 K. pneumoniae was circulating in humans for decades before the liver abscess epidemic was first recognised, and has the capacity to acquire and maintain AMR plasmids. These data provide a framework for future epidemiological and experimental studies of hypervirulent K. pneumoniae. To further support such studies we present an open access and completely sequenced human liver abscess isolate, SGH10, which is typical of the globally disseminated CG23-I sublineage.

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Section: Discussionmentioning

confidence: 99%

Section: Genome Collectionmentioning

confidence: 99%

Population genomics of hypervirulentKlebsiella pneumoniaeclonal group 23 reveals early emergence and rapid global dissemination

Wyres

Duchêne

Wick

et al. 2017

Preprint

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“…The K. pneumoniae isolates used in this study are clinical strains with a variety of antibiotic resistance markers, e.g., bla NDM-1 and bla SHV-18 , and have been described previously (9,10,44). K. pneumoniae was adapted to chlorhexidine as described in a previous study (9).…”

Section: Methodsmentioning

confidence: 99%

Mechanisms of Increased Resistance to Chlorhexidine and Cross-Resistance to Colistin following Exposure of Klebsiella pneumoniae Clinical Isolates to Chlorhexidine

Wand

Bock

Bonney

et al. 2017

Antimicrob Agents Chemother

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226

218

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Klebsiella pneumoniae is an opportunistic pathogen that is often difficult to treat due to its multidrug resistance (MDR). We have previously shown that K. pneumoniae strains are able to "adapt" (become more resistant) to the widely used bisbiguanide antiseptic chlorhexidine. Here, we investigated the mechanisms responsible for and the phenotypic consequences of chlorhexidine adaptation, with particular reference to antibiotic cross-resistance. In five of six strains, adaptation to chlorhexidine also led to resistance to the last-resort antibiotic colistin. Here, we show that chlorhexidine adaptation is associated with mutations in the two-component regulator phoPQ and a putative Tet repressor gene (smvR) adjacent to the major facilitator superfamily (MFS) efflux pump gene, smvA. Upregulation of smvA (10-to 27-fold) was confirmed in smvR mutant strains, and this effect and the associated phenotype were suppressed when a wild-type copy of smvR was introduced on plasmid pACYC. Upregulation of phoPQ (5-to 15-fold) and phoPQ-regulated genes, pmrD (6-to 19-fold) and pmrK (18-to 64-fold), was confirmed in phoPQ mutant strains. In contrast, adaptation of K. pneumoniae to colistin did not result in increased chlorhexidine resistance despite the presence of mutations in phoQ and elevated phoPQ, pmrD, and pmrK transcript levels. Insertion of a plasmid containing phoPQ from chlorhexidine-adapted strains into wild-type K. pneumoniae resulted in elevated expression levels of phoPQ, pmrD, and pmrK and increased resistance to colistin, but not chlorhexidine. The potential risk of colistin resistance emerging in K. pneumoniae as a consequence of exposure to chlorhexidine has important clinical implications for infection prevention procedures.

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“…1,2 The recent outbreaks of carbapenemase-producing K. Pneumonia are of great importance. [3][4][5] Chlorhexidine was first introduced commercially in the United Kingdom as a disinfectant and topical antiseptic in 1954.…”

mentioning

confidence: 99%

A Descriptive Study of Chlorhexidine as a Disinfectant in Cleft Palate Surgery

Roode¹,

Bütow²

2018

Clin Med Res

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Objectives:Chlorhexidine is seen as the golden standard of disinfectants. It is widely used to clean surgical sites; however, many studies indicate resistance of pathogens to chlorhexidine. One study indicated that pathogenic microorganisms were isolated from the soft palate cleft region in 57% of patients with facial clefts. The objectives of our study were to determine (1) if chlorhexidine application is effective in removing pathogens from the surgical site in these patients, and (2) if any pathogens are isolated, determine if they are resistant to other antimicrobials. Design:A descriptive observational study. Settings:A private practice that specializes in facial cleft surgery, with a country-wide patient base. All procedures were executed by one oral and maxillofacial surgeon.Participants: All patients (N=50) who presented for primary repair of the soft palate cleft were included in the study. Inclusion criteria: written consent from parent(s), and patient cleared as systemically healthy by a pediatric physician. Exclusion criteria: patient(s) with systemic infections (eg, flu) and/or any local infections (eg, tonsillitis). There were 25 males and 25 females with an average age of 7 months and 16 days included in the study.Methods: Swabs were taken from the surgical site of all 50 patients with cleft soft palate and were sent for culture, identification and antimicrobial sensitivity. The swabs were taken before disinfecting the site as well as after 2 minutes of disinfecting the surgical site with chlorhexidine. Results were compared against each other.Results: Positive cultures with 28 different pathogenic microorganisms that were identified in 47 patients before cleaning the surgical site with the chlorhexidine. The most dominant pathogens were K. pneumonia (n=22), H. influenza (n=18) and S. aureus (n=10). Of the pathogens found, 13 (46%) were still present on the swabs taken after disinfecting with chlorhexidine. K. pneumonia (n= 13), H. influenza (n=11) and S. aureus (n=9) were still the most prevalent pathogens. Conclusions:This study demonstrated that 61 of the total of 113 pathogens isolated (54%), survived after 2 minutes of disinfecting the surgical and surrounding area with chlorhexidine, thus intensifying the chances of post-operative infection.

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Characterization of Pre-Antibiotic Era Klebsiella pneumoniae Isolates with Respect to Antibiotic/Disinfectant Susceptibility and Virulence in Galleria mellonella

Cited by 59 publications

References 44 publications

Population genomics of hypervirulentKlebsiella pneumoniaeclonal group 23 reveals early emergence and rapid global dissemination

Population genomics of hypervirulentKlebsiella pneumoniaeclonal group 23 reveals early emergence and rapid global dissemination

Mechanisms of Increased Resistance to Chlorhexidine and Cross-Resistance to Colistin following Exposure of Klebsiella pneumoniae Clinical Isolates to Chlorhexidine

A Descriptive Study of Chlorhexidine as a Disinfectant in Cleft Palate Surgery

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