Turck, J. | bioRxiv Science

bioRxiv2026

Description of canine- and feline-derived strains of the bile acid-converting bacterium Peptacetobacter hiranonis: P. hiranonis subsp. deconjugans subsp. nov. and P. hiranonis subsp. nondeconjugans subsp. nov.

The bile acid-converting Peptacetobacter hiranonis is a Gram-positive, anaerobic, potentially spore-forming bacterium. It was first isolated from human feces and was subsequently shown to convert bile acids (BA) in both in vitro and in vivo experiments. The conversion of BA relies on the presence of the 7alpha-dehydroxylation multi-step pathway, encoded by the BA-inducible (bai) operon, harbored by P. hiranonis. In companion animals, P. hiranonis has been characterized as a biomarker for intestinal health, with its loss associated with dysbiosis. However, characterization of P. hiranonis cultured from companion animals is limited. An in-depth characterization of P. hiranonis was published by Chen et al. recently, including the proposal of a new species, Peptacetobacter hominis. We have sequenced the whole genome of both canine- and feline-derived strains of P. hiranonis, characterized these strains biochemically, and assessed their in vitro BA-converting ability as well as their antimicrobial resistance profiles. The strains described here can convert primary into secondary BAs and are whole-genome inhibited by low concentrations of amoxicillin-clavulanate, cefepime, ceftriaxone, chloramphenicol, ciprofloxacin, clindamycin, and metronidazole. Based on whole genome analysis, we propose dividing P. hiranonis into two host-adapted subspecies: P. hiranonis subsp. deconjugans and P. hiranonis subsp. nondeconjugans, based on their genomic differences and divergent ability to deconjugate BAs; a function that appears widely distributed among P. hiranonis strains cultured from dogs, but absent from those cultured from cats. Taken together, our results confirmed the BA conversion ability of P. hiranonis cultured from dogs and cats and reveal host-associated genomic and functional differences within the species.

microbiology↗

bioRxiv2022

Inositol Phosphorlyceramide Synthase null Leishmania major (Δipcs-) are viable and virulent in animal infections where salvage of host sphingomyelin predominates

Many pathogens synthesize inositolphosphorylceramide (IPC) as the major sphingolipid (SL), differing from the mammalian host where sphingomyelin (SM) or more complex SLs predominate, and the divergence between IPCS and mammalian sphingolipid synthases has prompted interest as a potential drug target. However, in the trypanosomatid protozoan Leishmania, cultured insect stage promastigotes lacking de novo sphingolipid synthesis ({Delta}spt2-) and sphingolipids entirely survive and remain virulent, as infective amastigotes salvage host sphingolipids and continue to produce IPC. To further understand the role of IPC, we generated null IPCS mutants in L. major ({Delta}ipcs-). Unexpectedly and unlike fungi where IPCS is essential, {Delta}ipcs- was remarkably normal in culture and highly virulent in mouse infections. Both IPCS activity and IPC were absent in {Delta}ipcs- promastigotes and amastigotes, arguing against an alternative route of IPC synthesis. Notably, salvaged mammalian sphingomyelin (SM) was highly abundant in purified amastigotes from both WT and {Delta}ipcs-, and salvaged SLs could be further metabolized into IPC. SM was about 7-fold more abundant than IPC in WT amastigotes, establishing that SM is the dominant amastigote SL, thereby rendering IPC partially redundant. These data suggest that SM salvage likely plays key roles in the survival and virulence of both WT and {Delta}ipcs- parasites in the infected host, confirmation of which will require the development of methods or mutants deficient in host SL/SM uptake in the future. Our findings call into question the suitability of IPCS as a target for chemotherapy, instead suggesting that approaches targeting SM/SL uptake or catabolism may warrant further emphasis.

microbiology↗