Pacemaker-Associated Infective Endocarditis Caused by Staphylococcus schleiferi

Rojas-Marte, Geurys; Victor, Joy; Shenoy, Amith; Yakubov, Stanley; Chapnick, Edward K.; Lin, Yu Shia

doi:10.1097/ipc.0000000000000179

Cited by 2 publications

(3 citation statements)

References 12 publications

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“…Red indicates a stop mutation at the site, while blue indicates a missense mutation. Schematic diagrams were prepared with the program Protter(5).…”

Section: Supporting Informationmentioning

confidence: 99%

“…coagulans , are leading causes of skin, soft tissue, and invasive infections in companion animals such as dogs and cats. In addition, these organisms cause zoonotic infections in humans that are clinically indistinguishable from infections with S. aureus including pneumonia, skin and soft tissue infections, hardware infections, and bacteremia(1–5). Newer clinical microbiological techniques, such as mass spectrometry, now readily distinguish S. aureus from zoonotic coagulase-positive staphylococci, which were previously often misidentified(3,6,7).…”

Section: Introductionmentioning

confidence: 99%

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Potent, specific MEPicides for treatment of zoonotic staphylococci

Edwards¹,

Heueck²,

Lee

et al. 2019

Preprint

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24Coagulase-positive staphylococci, which frequently colonize the mucosal surfaces of 25 animals, also cause a spectrum of opportunistic infections including skin and soft tissue 26 infections, urinary tract infections, pneumonia, and bacteremia. However, recent 27 45 robustly inhibit DXR in zoonotic staphylococci, and further, DXR represents a 46 promising, druggable target for future development. 3 47 48 Author Summary 49 The proliferation of microbial pathogens resistant to the current pool of antibiotics is a 50 major threat to public health. Drug resistance is pervasive in staphylococci, including 51 several species that can cause serious zoonotic infections in humans. Thus, new 52 antimicrobial agents are urgently need to combat these life-threatening, resistant 53 infections. Here we establish the MEP pathway as a promising new target against 54 zoonotic staphylococci. We determine that fosmidomycin (FSM) selectively targets the 55 isoprenoid biosynthesis pathway in zoonotic staphylococci, and use forward genetics to 56 identify the transporter that facilitates phosphonate antibiotic uptake. Employing this 57 knowledge, we synthesized a series of potent antibacterial prodrugs that circumvent 58 the transporter. Together, these novel prodrug inhibitors represent promising leads for 59 further drug development against zoonotic staphylococci. 60 61 65 zoonotic infections in humans that are clinically indistinguishable from infections with S. 66 aureus including pneumonia, skin and soft tissue infections, hardware infections, and 67 bacteremia(1-5). Newer clinical microbiological techniques, such as mass 68 spectrometry, now readily distinguish S. aureus from zoonotic coagulase-positive

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“…Red indicates a stop mutation at the site, while blue indicates a missense mutation. Schematic diagrams were prepared with the program Protter(5).…”

Section: Supporting Informationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Potent, specific MEPicides for treatment of zoonotic staphylococci

Edwards¹,

Heueck²,

Lee

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…coagulans, are leading causes of skin, soft tissue, and invasive infections in companion animals such as dogs and cats. In addition, these organisms cause zoonotic infections in humans that are clinically indistinguishable from infections with S. aureus including pneumonia, skin and soft tissue infections, hardware infections, and bacteremia [1][2][3][4][5]. Newer clinical microbiological techniques, such as mass spectrometry, now readily distinguish S. aureus from zoonotic coagulase-positive staphylococci, which were previously often misidentified [3,6,7].…”

Section: Introductionmentioning

confidence: 99%

Potent, specific MEPicides for treatment of zoonotic staphylococci

et al. 2020

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Coagulase-positive staphylococci, which frequently colonize the mucosal surfaces of animals, also cause a spectrum of opportunistic infections including skin and soft tissue infections, urinary tract infections, pneumonia, and bacteremia. However, recent advances in bacterial identification have revealed that these common veterinary pathogens are in fact zoonoses that cause serious infections in human patients. The global spread of multidrugresistant zoonotic staphylococci, in particular the emergence of methicillin-resistant organisms, is now a serious threat to both animal and human welfare. Accordingly, new therapeutic targets that can be exploited to combat staphylococcal infections are urgently needed. Enzymes of the methylerythritol phosphate pathway (MEP) of isoprenoid biosynthesis represent potential targets for treating zoonotic staphylococci. Here we demonstrate that fosmidomycin (FSM) inhibits the first step of the isoprenoid biosynthetic pathway catalyzed by deoxyxylulose phosphate reductoisomerase (DXR) in staphylococci. In addition, we have both enzymatically and structurally determined the mechanism by which FSM elicits its effect. Using a forward genetic screen, the glycerol-3-phosphate transporter GlpT that facilitates FSM uptake was identified in two zoonotic staphylococci, Staphylococcus schleiferi and Staphylococcus pseudintermedius. A series of lipophilic ester prodrugs (termed PLOS PATHOGENS

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Pacemaker-Associated Infective Endocarditis Caused by Staphylococcus schleiferi

Cited by 2 publications

References 12 publications

Potent, specific MEPicides for treatment of zoonotic staphylococci

Potent, specific MEPicides for treatment of zoonotic staphylococci

Potent, specific MEPicides for treatment of zoonotic staphylococci

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