bioRxiv Science⌕ Search

bioRxiv · 10.1101/2022.04.18.488710

Route of oxytetracycline administration differentially impacts the growth and gut microbiome of pigs co-infected with Bordetella bronchiseptica and Pasteurella multocida

Abstract

Along with judicious antibiotic use, there is great interest in how the dose regimen of an antibiotic affects the animal gut microbiota. This study evaluated the impact of experimental respiratory infection alone or respiratory infection followed by oxytetracycline (oxytet) treatment on the animals health and its fecal microbiome. Piglets of approximately three weeks-of-age were separated into four groups (n=20 per group). One group remained non-infected and administered non-medicated feed and the other three groups were infected with Bordetella bronchiseptica (day 0) and Pasteurella multocida (day 4), with one group receiving non- medicated feed and the remaining two groups receiving oxytetr starting on day 7 by injection or in-feed (day 7-14). Infection with B. bronchiseptica and P. multocida negatively impacted piglet growth and induced mild pneumonia. Infection alone had minimal effect on the fecal microbiota community. When oxytet was administered either by injection or in-feed to treat the respiratory infections, both routes had minimal effect on clearing B. bronchiseptica and P. multocida in the animal. However, both routes appeared to limit lung lesion severity, and injected oxytet reduced the negative impact of infection on weight gain. Both routes had limited impact on the animals overall gut microbiome, including relative abundances of bacterial taxa and antibiotic resistance genes tet32, tetW, and aph2. Overall, oxytet administered by either route did not clear the respiratory infection, but oxytet administration minimized the negative health impacts of infection and had minor impact on the pig gut microbiome. ImportanceEfforts to address antibiotic resistance calls for improved antibiotic stewardship, including considering antibiotic administration route. While our previous study found in-feed oxytet had greater impact on the gut microbiome of healthy piglets than injected oxytet, it remained unknown if oxytet treatments would have the same impact on the microbiota of infected piglets. We evaluated the impact of respiratory infection alone or respiratory infection followed by oxytet treatment on the animals health and their gut microbiome profile. Respiratory infection negatively affected piglets health, but infection alone had minimal impact on the gut community. When oxytet was administered either in-feed or by injection to treat the respiratory infection, neither route of administration led to the clearance of the respiratory pathogens. However, oxytet minimized the negative health impacts of infection, and had minor impact on the pig gut microbiome. These findings are informative for disease management in food animals while integrating antibiotic stewardship practices.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Mou, K., Trachsel, J., Stephens, A., Ricker, N., Brockmeier, S. L., Allen, H. K., Loving, C. L.. 2022-04-19. Route of oxytetracycline administration differentially impacts the growth and gut microbiome of pigs co-infected with Bordetella bronchiseptica and Pasteurella multocida. https://doi.org/10.1101/2022.04.18.488710

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

KEEP EXPLORING

Related preprints

A conserved cysteine-histidine-glutamate metal site identifies DUF501 (Rv1025), an essential uncharacterised protein family of Mycobacterium tuberculosis, as a candidate metalloenzyme and drug target

A substantial fraction of the Mycobacterium tuberculosis proteome remains functionally uncharacterised. Rv1025, a 155-residue protein carrying the domain of unknown function DUF501 (Pfam PF04417), is essential by transposon mutagenesis and vulnerable by CRISPR interference, an attractive but neglected drug target, yet has never been functionally described. The family (4,370 proteins, no Gene Ontology term, no solved structure) is uncharacterised across all organisms and essential in three Actinobacterial genera. A Foldseek search of the AlphaFold model against complete structural databases finds no significant homolog, indicating a novel fold. The operon eno-divIC-Rv1025-ppx2 is conserved across the Actinobacteria phylum, yet AlphaFold-Multimer finds no direct complex between Rv1025 and its neighbour DivIC. Instead, conservation across 8,700 homologous sequences reveals a near-invariant Cys113-His115-Glu59 cluster forming a pocket. Holo AlphaFold3 predictions with Zn, Fe and Mn confidently place a divalent metal on this triad at 2.25-2.47 A; mutating the triad relocates the metal, and an independent backbone-geometry predictor recovers the same site, confirming specificity. The triad is universal across the family: present in all 1,472 near-complete bacterial sequences of the Pfam alignment, with no non-conservative substitution among the 2,228 sequences examined, a defining feature of bacterial DUF501 rather than a mycobacterial peculiarity. We propose that DUF501 is a metal-binding protein and candidate metalloenzyme, the first functional hypothesis for this family, whose conserved, essential metal pocket is a promising drug target. As the predictions build on a conservation-defined site within a fully computational study, they are supportive rather than proof of metal occupancy and warrant experimental validation.

microbiology↗

Mycoplasmal endosymbionts of Trichomonas vaginalis are associated with reduced risk for Chlamydia trachomatis endometrial infection in asymptomatic, coinfected, women.

Trichomonas vaginalis is a protozoan parasite that causes trichomoniasis, the most common curable non-viral sexually transmitted infection, and Chlamydia trachomatis is a bacterial pathogen that can ascend to the upper genital tract and cause pelvic inflammatory disease, infertility, and ectopic pregnancy. T. vaginalis harbors bacterial endosymbionts, including Candidatus Malacoplasma girerdii, an obligate symbiont, and Metamycoplasma hominis, which can live freely or symbiotically. In a 16S rRNA sequencing study of the cervicovaginal microbiome of women at high risk for chlamydial infection, Ca. M. girerdii abundance was one of 13 features predicting lack of chlamydial spread to the endometrium, despite no direct association between T. vaginalis infection and reduced chlamydial ascension. Investigating the relationship between these microorganisms further, we found that T. vaginalis vaginal abundance correlated positively with chlamydial burden in women whose infection was confined to the cervix, while a nonsignificant inverse relationship was seen in women with endometrial spread. Among participants with high chlamydial burden, Ca. M. girerdii was detected exclusively in women without endometrial infection. Both endosymbionts trended toward more frequent detection, and higher abundance, in coinfected women without endometrial spread, while M. hominis abundance correlated strongly with T. vaginalis burden in this group. These findings suggest that mycoplasmal endosymbionts of T. vaginalis, rather than T. vaginalis itself, are microbial factors limiting chlamydial ascension, and point to a three-way interaction between parasite, endosymbiont, and bacterial pathogen that shapes upper genital tract C. trachomatis infection risk.

microbiology↗

Understanding the physiological alterations of Vibrio cholerae upon exposure to L-ascorbic acid

The scourge of cholera remains a major global public health threat. It affects up to 4 million people worldwide and causes tens of thousands of deaths each year. The disease is experiencing a concerning resurgence in many parts of Africa, the Middle East, and Asia. To effectively tackle cholera and circumvent rising antimicrobial resistance, targeted biological and preventive approaches, complementing traditional rehydration, are urgently needed. In this regard, our group has demonstrated the efficacy of L-ascorbic acid in controlling the growth and pathogenesis of Vibrio cholerae in vitro. The present work further provides a mechanistic elucidation of the L-ascorbic acid-mediated physiological changes in V. cholerae and also bolsters such a non-antibiotic approach to control cholera.

microbiology↗