Need For CF Patients To Avoid Staphylococcus Aureus Underscored By New Research

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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CF patient avoiding MRSA

CF patient avoiding MRSAA new study entitled “Inter- and Intraspecies Metabolite Exchange Promotes Virulence of Antibiotic-Resistant Staphylococcus aureus” published in Cell Host & Microbe reports antibiotic-resistant Staphylococcus aureus interacts with other species to promote their growth and virulence inside its host. This new finding is particularly important to the CF community, since Staphylococcus aureus infections are among the most serious for those with the disease.

Staphylococcus aureus is an important threat to clinical therapeutics with the emergence of antibiotic-resistant forms of S. aureus, commonly noted as MRSA, accounting for 50% of antibiotic-resistance associated deaths. In patients with cystic fibrosis (CF) — a genetic disorder frequently escalating to lung infections – Staphylococcus aureus is one of the three most common organisms in CF lung infections and is associated with advanced pulmonary disease. Thus, understanding the mechanisms of Staphylococcus aureus resistance is particularly important for CF patients. To be able to resist to antibiotics, S. aureus and other pathogens change to a respiration-deficient state known as a small colony variant (SCV). While this allows pathogens to resist antibiotics, it poses a fitness defect when compared to wild type, with impaired growth and production of virulence factors. It is still unclear, however, what the mechanisms are that allow SCVs and other antibiotic-resistant bacteria to persist and cause disease.

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Staphylococcus AureusIn this study, a team of scientists from the Department of Pathology, Microbiology, and Immunology at Vanderbilt University School of Medicine in Nashville, and collaborators, found fitness reduction associated with one resistance-conferring mutation can be counterbalanced by interacting with other genetically different microorganisms. The authors demonstrated by two different approaches – cocultures and coinfection – that distinct S. aureus strains can exchange metabolites with each other to overcome the fitness cost derived from resistance-mutations. Notably, they extended their findings and showed that these interactions also occurred with the human microbiome. Thus, the metabolite exchange between both intra and inter-species allows for antibiotic-resistant Staphylococcus aureus to enhance their growth and virulence.

Eric Skaar, Ph.D., MPH, Ernest W. Goodpasture Professor of Pathology, Microbiology and Immunology and lead author of the study commented, “The microbiome of a cystic fibrosis patient’s lungs can provide nutrients to these small colony variants and revert them to wild-type behavior. Our findings show that these antibiotic-resistant infections are not what we thought they were — they’re not a single strain of bacteria with a single lesion leading to the small colony variant phenotype. Instead, they’re a mixed population of organisms that are sharing nutrients. They act like a big group of bullies until you hit them with drugs, then they stop sharing resources and are resistant. When the drugs go away, they start sharing resources again and get even tougher. We’re now a little bit smarter about how these organisms are behaving in an infection, which I think we can use to inform new treatment approaches.”

These findings have clear implications for diagnosis and treatment of infections caused by SCVs. The authors suggest that preventing nutrient exchange might be a promising new therapeutic strategy against SCVs.