Host-Targeted Therapeutics against Multidrug Resistant Intracellular Staphylococcus aureus.

Natalia Bravo-Santano,Volker Behrends,Michal Letek

doi:10.3390/antibiotics8040241

Natalia Bravo-Santano, Volker Behrends + Show 1 more

Open Access

https://doi.org/10.3390/antibiotics8040241

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Journal: Antibiotics	Publication Date: Nov 28, 2019
Citations: 9	License type: CC BY 4.0

Affiliation: University of Roehampton, University of Leon

Abstract

Staphylococcus aureus is a facultative intracellular pathogen that invades and replicates within many types of human cells. S. aureus has shown to rapidly overcome traditional antibiotherapy by developing multidrug resistance. Furthermore, intracellular S. aureus is protected from the last-resort antibiotics—vancomycin, daptomycin, and linezolid—as they are unable to achieve plasma concentrations sufficient for intracellular killing. Therefore, there is an urgent need to develop novel anti-infective therapies against S. aureus infections. Here, we review the current state of the field and highlight the exploitation of host-directed approaches as a promising strategy going forward.

Highlights

Health Sciences Research Centre, University of Roehampton, London SW15 4JD, UK; Department of Molecular Biology, Area of Microbiology, University of León, 24004 León, Spain
Many staphylococcal infections are caused by strains that are resistant to multiple antibiotics, which are associated with higher costs and extended hospitalization periods, as well as higher morbidity and mortality rates [5]
Isolates are susceptible to most antimicrobials apart from β-lactam antibiotics and erythromycin, whereas hospital-acquired Methicillin-Resistant Staphylococcus aureus (MRSA) (HA-MRSA) isolates are resistant to most available antibiotics [9]

Summary

Intracellular MRSA Is Protected from Common Antibiotic Treatments

The opportunistic and facultative intracellular pathogen S. aureus is carried by 30% of the global population [10,11], the anterior nares of the nasal cavity being the most common carriage site [12,13]. The current list of antibiotics available and approved to treat MRSA infections are vancomycin, daptomycin, linezolid, and some other antimicrobials that have been recently developed, including tedizolid, telavancin, oritavancin, dalbavancin, ceftaroline, and ceftobiprole [23]. These latter antibiotics are mostly employed to treat skin and soft tissue infections, with vancomycin, daptomycin, and linezolid being the top options for non-topical and/or systemic infections. The use of antibiotics targeting cell growth or division of the pathogen is still a major selective pressure towards the emergence of resistant strains

Host-Directed Therapies: A Novel Perspective

Findings

Conclusions