Campylobacter Abundance in Breastfed Infants and Identification of a New Species in the Global Enterics Multicenter Study

Abstract

Campylobacter jejuni is a leading cause of bacterial diarrhea worldwide and is associated with high rates of mortality and growth stunting in children inhabiting low- to middle-resource countries. To better understand the impact of breastfeeding on Campylobacter infection in infants in sub-Saharan Africa and South Asia, we examined fecal microbial compositions, bacterial isolates, and their carbohydrate metabolic pathways in Campylobacter-positive infants <1 year of age from the Global Enterics Multicenter Study. Exclusively breastfed infants with diarrhea exhibited high Campylobacter abundances, and this negatively correlated with bacterial carbohydrate metabolism. Although C. jejuni and Campylobacter coli are prevalent among these infants, the second most abundant Campylobacter species was a new species, which we named “Candidatus Campylobacter infans.” Asymptomatic Campylobacter carriers also possess significantly different proportions of specific gut microbes compared to diarrheal cases. These findings provide insight into Campylobacter infections in infants in sub-Saharan Africa and South Asia and help inform strategies aimed at eliminating campylobacteriosis in these areas. IMPORTANCE Campylobacter is the primary cause of bacterial diarrhea in the United States and can lead to the development of the postinfectious autoimmune neuropathy known as Guillain-Barré syndrome. Also, drug-resistant campylobacters are becoming a serious concern both locally and abroad. In low- and middle-income countries (LMICs), infection with Campylobacter is linked to high rates of morbidity, growth stunting, and mortality in children, and breastfeeding is important for infant nutrition, development, and protection against infectious diseases. In this study, we examined the relationship between breastfeeding and Campylobacter infection and demonstrate the increased selection for C. jejuni and C. coli strains unable to metabolize fucose. We also identify a new Campylobacter species coinfecting these infants with a high prevalence in five of the seven countries in sub-Saharan Africa and South Asia examined. These findings indicate that more detailed studies are needed in LMICs to understand the Campylobacter infection process in order to devise a strategy for eliminating this pathogenic microbe.

Bacteroides fragilis fucosidases facilitate growth and invasion of Campylobacter jejuni in the presence of mucins

“…Furthermore, we used activity‐based protein profiling (ABPP) and chemical competitive inhibitors to demonstrate the crucial contribution of these exogenous fucosidases to the increased invasion by C. jejuni 108 into intestinal epithelial cells. Our findings complement two recent publications on the topic of C. jejuni fuc + strains that investigated nutrient scavenging by C. jejuni fuc + strains and demonstrated how the presence of glycoproteins in human milk affects the selection of these specific strains (Bian et al, 2020; Garber et al, 2020). Furthermore, it is interesting to speculate that our data are in line with a previous finding that individuals with higher proportions of Bacteroides species are more susceptible to C. jejuni infections (Dicksved, Ellström, Engstrand, & Rautelin, 2014).…”

Complete Genome Sequence of a Clinical Campylobacter Isolate Identical to a Novel Campylobacter Species

“…The sequence clustered with the genome of the recently identified novel putative species belonging to the Campylobacter fetus group “ Candidatus Campylobacter infans” ( Fig. 1 ) ( 7 ) with a 98.27% ANI.…”

“…This resulted in two circular contigs, representing a 1,754.5-kb chromosome with a GC content of 35.9% and a 5,856-kb plasmid. Prokka v1.13 ( 6 ) was used for annotation with “ Candidatus Campylobacter infans” as an additional custom database (GenBank accession number SPMW00000000.1 ) ( 7 , 8 ). A core genome phylogeny without correction for recombination was reconstructed using FastTree ( 9 ), based on a 365,157-bp core gene superalignment of 351 core genes of which the protein sequences had at least 35% sequence identity, as determined by Roary v3.12.0 ( 10 ).…”

“…A putative integrated phage containing genes for a type IV (T4SS) conjugative transfer system ( 13 ) and a second phage integration containing a zonula occludens toxin (Zot) island were identified. The S-layer secretion system gene sapDEF , as well as d -arabinose 5-phosphate isomerase ( kpsF ), and flagellin-associated genes were present as identified in the genome of “ Candidatus Campylobacter infans” ( 7 ). This study shows the first complete genome and plasmid sequences of a clinical isolate with high sequence identity to a novel Campylobacter species.…”

Transient Effect of Infant Formula Supplementation on the Intestinal Microbiota

“…Previously, breast milk was thought to protect infants against Campylobacter infection due to the presence of antibodies and human milk oligosaccharides in breast milk [ 62 , 63 ]. However, in sub-Saharan African and South Asian infants, Campylobacter abundance was shown to be correlated with breastfeeding, and resulted in more diarrhea cases in breastfed infants [ 64 ]. The increase of Campylobacter was also observed in breastfed Rhesus macaque compared to that in bottle-fed animals, which correlated with the increase in arachidonic acid present in the stool and was hypothesized to contribute to T H 17 cell expansion [ 59 ].…”