Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/512616

The gut microbiota is associated with clearance of Clostridium difficile infection independent of adaptive immunity

Leslie, J. L.·Vendrov, K. C.·Jenior, M. L.·Young, V. B.
View original source ↗Export metadata ↓

Abstract

Clostridium (Clostridioides) difficile, a Gram-positive, anaerobic bacterium is the leading single cause of nosocomial infections in the United States. A major risk factor for C. difficile infection (CDI) is prior exposure to antibiotics as they increase susceptibility to CDI by altering the membership of the microbial community enabling colonization. The importance of the gut microbiota in providing protection from CDI is underscored by the reported 80-90% success rate of fecal microbial transplants in treating recurrent infection. Adaptive immunity, specifically humoral immunity, is also sufficient to protect from both acute and recurrent CDI. However, the role of the adaptive immune system in mediating clearance of C. difficile has yet to be resolved. Using murine models of CDI, we found that adaptive immunity is dispensable for clearance of C. difficile. However, Random Forest analysis using only 2 members of the resident bacterial community correctly identified animals that would go on to clear the infection with 66.7% accuracy. These findings indicate that the indigenous gut microbiota independent of adaptive immunity facilitates clearance of C. difficile from the murine gastrointestinal tract.\n\nImportanceC. difficile infection is a major cause of morbidity and mortality in hospitalized patients in the United States. Currently the role of the adaptive immune response in modulating levels of C. difficile colonization is unresolved. This work suggests that the indigenous gut microbiota is a main factor that promotes clearance of C. difficile from the GI tract. Our results show that clearance of C. difficile can occur without contributions from the adaptive immune response. This study also has implications for the design of preclinical studies testing the efficacy of vaccines on clearance of bacterial pathogens as inherent differences in the baseline community structure of animals may bias findings.

Source connections

Explore related subjects

microbiologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Leslie, J. L., Vendrov, K. C., Jenior, M. L., Young, V. B.. 2019-01-06. The gut microbiota is associated with clearance of Clostridium difficile infection independent of adaptive immunity. https://doi.org/10.1101/512616

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Cell-scale confinement reorders bacterial speed rankings

Which bacterium swims fastest depends on where the race is run. Speeds are usually measured in open liquid, yet many bacteria live in pores, mucus and host passages no wider than a cell. Using a microfluidic device with eight channel widths (0.80-3.00 m) in one field of view, we tracked unlabeled cells of eight species spanning five motility systems. Chamber height, a polymer additive and channel width each reordered the ranking. Vibrio alginolyticus, the fastest in open liquid, slowed to ~4 m/s in 1.25-m channels, whereas Campylobacter jejuni and Bacillus subtilis kept 33-46 m/s. Open liquid speed did not predict robustness to confinement. In two unrelated lineages, host symbionts that pass through narrow passages during colonization, Caballeronia insecticola and Vibrio fischeri, outran their non-symbiotic relatives in the channels, and crossed them with flagella wrapped around the cell body at nearly the speed of unwrapped cells. Where space is tight, the ability to keep moving, not top speed, sets the ranking.

microbiology↗
bioRxiv2026

The biochemical composition of coronavirus Nucleocapsid proteins drives the bicistronic properties of their sub-genomic mRNAs

The nucleocapsid (N) gene of coronaviruses (CoVs) encodes a structural RNA-binding protein required for viral assembly. In SARS- and MERS-CoV viruses, reading frame 2 of N contains an overlapping open reading frame (ORF) encoding an innate immune antagonist accessory protein. However, the extent of this dual coding capacity across the CoV family, and the genetic features driving overlapping ORF formation, remain unexamined. Here, we developed an in-silico tool (ORFan) to screen structural gene sub-genomic mRNA sequences from 152 species of coronavirus for the presence of overlapping accessory gene candidates. We found that frame 2 of the N gene in Alpha-, Beta- and Delta-CoVs frequently contains a potential accessory ORF (AcORF), conserved at the subgenus level, unlike the spike, envelope and membrane genes. We also show that CoV nucleotide biases in conjunction with codon biases integral to N protein function drive the relatively high abundances of start codons in frame two and stop codons in frame three, explaining the tendency towards frame 2 AcORFs. We further suggest that viral nucleotide biases and the codon composition required for RNA-binding function facilitate overlapping ORF formation in other virus families

microbiology↗
bioRxiv2026

Evaluating non-oxidative glycolysis using 13C metabolic flux analysis

Non-oxidative glycolysis (NOG) converts glucose to acetyl-CoA without emitting CO2 during Escherichia coli bioproduction. Although 13C-metabolic flux analysis (13C-MFA) has the potential to evaluate NOG flux distribution in vivo, the precision of these estimates depends on the labeling patterns of glucose tracers. Because E. coli has multiple native glycolysis pathways, selecting the optimal glucose tracer is important for precise estimates. This study used simulations to evaluate the performance of 18 commercially available glucose tracers in precisely predicting NOG flux. We artificially generated flux distributions of central metabolic pathways, including three types of NOG pathways, and obtained 13C labeling patterns of amino acids metabolized from each glucose tracer. Using these data, we then calculated 95% confidence intervals (CIs) for NOG pathway fluxes. Comparing the sum of CI widths from three NOG fluxes showed that estimation with [1,3-13C]-glucose yielded the narrowest CIs. Several tracers, including [2,3-13C]glucose, were capable of determining fluxes with high precision, but [1-13C]glucose was not one of them, despite often being used for estimating glycolytic fluxes. We then experimentally evaluated [2,3-13C]- and [1-13C]glucose as tracers in E. coli strains with and without the expression of phosphoketolase, which is required for NOG pathways to function. The results suggested that [1-13C]glucose could not detect NOG fluxes, whereas [2,3-13C]glucose estimated the fluxes of all three NOG pathways with narrow CIs.

microbiology↗