Divergent Isoprenoid Biosynthesis Pathways in <italic toggle="yes">Staphylococcus</italic> Species Constitute a Drug Target for Treating Infections in Companion Animals

ABSTRACT Staphylococcus species are a leading cause of skin and soft tissue infections in humans and animals, and the antibiotics used to treat these infections are often the same. Methicillin- and multidrug-resistant staphylococcal infections are becoming more common in human and veterinary medicin...

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Autores principales:	Ana M. Misic, Christine L. Cain, Daniel O. Morris, Shelley C. Rankin, Daniel P. Beiting
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Staphylococcus companion animals comparative genomics fosmidomycin isoprenoid biosynthesis One Health Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c6126e08cd1341dbbf2c5dccf6b05a8e
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spelling	oai:doaj.org-article:c6126e08cd1341dbbf2c5dccf6b05a8e2021-11-15T15:21:30ZDivergent Isoprenoid Biosynthesis Pathways in <italic toggle="yes">Staphylococcus</italic> Species Constitute a Drug Target for Treating Infections in Companion Animals10.1128/mSphere.00258-162379-5042https://doaj.org/article/c6126e08cd1341dbbf2c5dccf6b05a8e2016-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00258-16https://doaj.org/toc/2379-5042ABSTRACT Staphylococcus species are a leading cause of skin and soft tissue infections in humans and animals, and the antibiotics used to treat these infections are often the same. Methicillin- and multidrug-resistant staphylococcal infections are becoming more common in human and veterinary medicine. From a “One Health” perspective, this overlap in antibiotic use and resistance raises concerns over the potential spread of antibiotic resistance genes. Whole-genome sequencing and comparative genomics analysis revealed that Staphylococcus species use divergent pathways to synthesize isoprenoids. Species frequently associated with skin and soft tissue infections in companion animals, including S. schleiferi and S. pseudintermedius, use the nonmevalonate pathway. In contrast, S. aureus, S. epidermidis, and S. lugdunensis use the mevalonate pathway. The antibiotic fosmidomycin, an inhibitor of the nonmevalonate pathway, was effective in killing canine clinical staphylococcal isolates but had no effect on the growth or survival of S. aureus and S. epidermidis. These data identify an essential metabolic pathway in Staphylococcus that differs among members of this genus and suggest that drugs such as fosmidomycin, which targets enzymes in the nonmevalonate pathway, may be an effective treatment for certain staphylococcal infections. IMPORTANCE Drug-resistant Staphylococcus species are a major concern in human and veterinary medicine. There is a need for new antibiotics that exhibit a selective effect in treating infections in companion and livestock animals and that would not be used to treat human bacterial infections. We have identified fosmidomycin as an antibiotic that selectively targets certain Staphylococcus species that are often encountered in skin infections in cats and dogs. These findings expand our understanding of Staphylococcus evolution and may have direct implications for treating staphylococcal infections in veterinary medicine.Ana M. MisicChristine L. CainDaniel O. MorrisShelley C. RankinDaniel P. BeitingAmerican Society for MicrobiologyarticleStaphylococcuscompanion animalscomparative genomicsfosmidomycinisoprenoid biosynthesisOne HealthMicrobiologyQR1-502ENmSphere, Vol 1, Iss 5 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Staphylococcus companion animals comparative genomics fosmidomycin isoprenoid biosynthesis One Health Microbiology QR1-502
spellingShingle	Staphylococcus companion animals comparative genomics fosmidomycin isoprenoid biosynthesis One Health Microbiology QR1-502 Ana M. Misic Christine L. Cain Daniel O. Morris Shelley C. Rankin Daniel P. Beiting Divergent Isoprenoid Biosynthesis Pathways in <italic toggle="yes">Staphylococcus</italic> Species Constitute a Drug Target for Treating Infections in Companion Animals
description	ABSTRACT Staphylococcus species are a leading cause of skin and soft tissue infections in humans and animals, and the antibiotics used to treat these infections are often the same. Methicillin- and multidrug-resistant staphylococcal infections are becoming more common in human and veterinary medicine. From a “One Health” perspective, this overlap in antibiotic use and resistance raises concerns over the potential spread of antibiotic resistance genes. Whole-genome sequencing and comparative genomics analysis revealed that Staphylococcus species use divergent pathways to synthesize isoprenoids. Species frequently associated with skin and soft tissue infections in companion animals, including S. schleiferi and S. pseudintermedius, use the nonmevalonate pathway. In contrast, S. aureus, S. epidermidis, and S. lugdunensis use the mevalonate pathway. The antibiotic fosmidomycin, an inhibitor of the nonmevalonate pathway, was effective in killing canine clinical staphylococcal isolates but had no effect on the growth or survival of S. aureus and S. epidermidis. These data identify an essential metabolic pathway in Staphylococcus that differs among members of this genus and suggest that drugs such as fosmidomycin, which targets enzymes in the nonmevalonate pathway, may be an effective treatment for certain staphylococcal infections. IMPORTANCE Drug-resistant Staphylococcus species are a major concern in human and veterinary medicine. There is a need for new antibiotics that exhibit a selective effect in treating infections in companion and livestock animals and that would not be used to treat human bacterial infections. We have identified fosmidomycin as an antibiotic that selectively targets certain Staphylococcus species that are often encountered in skin infections in cats and dogs. These findings expand our understanding of Staphylococcus evolution and may have direct implications for treating staphylococcal infections in veterinary medicine.
format	article
author	Ana M. Misic Christine L. Cain Daniel O. Morris Shelley C. Rankin Daniel P. Beiting
author_facet	Ana M. Misic Christine L. Cain Daniel O. Morris Shelley C. Rankin Daniel P. Beiting
author_sort	Ana M. Misic
title	Divergent Isoprenoid Biosynthesis Pathways in <italic toggle="yes">Staphylococcus</italic> Species Constitute a Drug Target for Treating Infections in Companion Animals
title_short	Divergent Isoprenoid Biosynthesis Pathways in <italic toggle="yes">Staphylococcus</italic> Species Constitute a Drug Target for Treating Infections in Companion Animals
title_full	Divergent Isoprenoid Biosynthesis Pathways in <italic toggle="yes">Staphylococcus</italic> Species Constitute a Drug Target for Treating Infections in Companion Animals
title_fullStr	Divergent Isoprenoid Biosynthesis Pathways in <italic toggle="yes">Staphylococcus</italic> Species Constitute a Drug Target for Treating Infections in Companion Animals
title_full_unstemmed	Divergent Isoprenoid Biosynthesis Pathways in <italic toggle="yes">Staphylococcus</italic> Species Constitute a Drug Target for Treating Infections in Companion Animals
title_sort	divergent isoprenoid biosynthesis pathways in <italic toggle="yes">staphylococcus</italic> species constitute a drug target for treating infections in companion animals
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/c6126e08cd1341dbbf2c5dccf6b05a8e
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Divergent Isoprenoid Biosynthesis Pathways in <italic toggle="yes">Staphylococcus</italic> Species Constitute a Drug Target for Treating Infections in Companion Animals

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