High-resolution microbiome analysis reveals exclusionary Klebsiella species competition in preterm infants at risk for necrotizing enterocolitis

Abstract

Intestinal colonization with Klebsiella has been linked to necrotizing enterocolitis (NEC), but methods of analysis usually failed to discriminate Klebsiella species or strains. A novel ~ 2500-base amplicon (StrainID) that spans the 16S and 23S rRNA genes was used to generate amplicon sequence variant (ASV) fingerprints for Klebsiella oxytoca and Klebsiella pneumoniae species complexes (KoSC and KpSC, respectively) and co-occurring fecal bacterial strains from 10 preterm infants with NEC and 20 matched controls. Complementary approaches were used to identify cytotoxin-producing isolates of KoSC. Klebsiella species colonized most preterm infants, were more prevalent in NEC subjects versus controls, and replaced Escherichia in NEC subjects. Single KoSC or KpSC ASV fingerprinted strains dominated the gut microbiota, suggesting exclusionary Klebsiella competition for luminal resources. Enterococcus faecalis was co-dominant with KoSC but present infrequently with KpSC. Cytotoxin-producing KoSC members were identified in most NEC subjects and were less frequent in controls. Few Klebsiella strains were shared between subjects. We conclude that inter-species Klebsiella competition, within an environment of KoSC and E. faecalis cooperation, appears to be an important factor for the development of NEC. Preterm infants seem to acquire Klebsiella primarily through routes other than patient-to-patient transmission.

Unexpected decrease in necrotizing enterocolitis morbidity during the COVID-19 pandemic-A single-centre retrospective study

“…The reasons for these different conclusions may be the heterogeneity among studies, including study size, study design, different pandemic-related measures, and differences in participant selection, such as birth weight, gestational age and severity of illness. Environmental factors may influence the development of NEC (20). The factor most likely to explain the decrease in NEC morbidity in our study is compliance with preventative measures to reduce bacterial and viral transmission.…”

“…Environmental factors may influence the development of NEC ( 20 ). The factor most likely to explain the decrease in NEC morbidity in our study is compliance with preventative measures to reduce bacterial and viral transmission.…”

Core genome multilocus sequence typing (cgMLST) applicable to the monophyletic Klebsiella oxytoca species complex

“…The presence of the til gene cluster is a valuable genetic marker, since the toxicity of strains has been linked to AAHC in previous studies ( 22 , 23 ) and has been associated with NEC ( 5 , 25 ). Presence of til genes was compared to strain toxicity as evaluated by MTT assays.…”

“…Of particular concern is that both species show increasing rates of multidrug resistance and even share virulence factors ( 3 ). Particularly in healthcare-associated outbreaks, K. oxytoca poses a significant threat by nosocomial transmission of extended-spectrum-β-lactamase producing K. oxytoca in intensive care units (ICUs) ( 4 ) or infection of neonates in neonatal intensive care units ( 5 ). Such outbreaks and transmission events are particularly difficult to manage due to the persistence of the bacteria in and spread via environmental reservoirs ( 6 ) and opportunistic presence in humans ( 7 , 8 ).…”

Antimicrobial susceptibility profile of Klebsiella pneumoniae isolated from some dairy products in Libya as a foodborne pathogen

“…Klebsiella species have been associated with necrotizing enterocolitis in infants, as documented by Coleman et al . [ 37 ]. These species have been classified as category B organisms and are intended to cause infections in infants.…”