Prophages Can Prevent Invasiveness of S aureus Growth in Diabetic Foot Ulcers

Patients with diabetic foot ulcers infected with Staphylococcus aureus may be helped by the presence of specific prophages, which can reduce S aureus invasiveness by limiting intracellular growth, according to a study published in the Journal of Infectious Diseases.¹

Jean-Phillippe Rasigade, MD, PhD, at the International Center for Infectiology Research at Ecole Normale Supérieure de Lyon at the University of Lyon, France, and colleagues examined the S aureas isolate NSA 1385 from an uninfected diabetic foot ulcer (DFU) along with its isogenic ROSA-like negative variant. The ROSA-like negative variant (Δrosa) was obtained following ROSA-like expulsion in a trace mineral supplement medium that had restricted iron growth conditions.

Researchers used cell invasion assay and statistical analysis to compare the amount of intracellular bacteria contained within osteoblasts that were infected with NSA 1385 and the Δrosa variant following 3, 24, and 48 hours of incubation.

“We observed that ROSA-like expulsion correlated with an enhanced ability to grow in the intracellular compartment,” Dr Rasigade and colleagues reported. “The proportion of the infecting inoculum that survived within osteoblasts was higher at all [examined] time points in ∆rosa strain compared to NSA1385,” they said, noting that time increased the difference 1.6, 2.6, and 5.6 fold at each increment of hours.

They noted that the pattern related to NSA 1385’s lack of ability to grow in osteoblast but did not affect the Δrosa variant. Researchers said that in “a multiple regression of relative intracellular model colony forming units,” adjusted for the length of incubation and inter-experiment differences, that “the inclusion of ROSA-like positivity (NSA 1385 vs ∆rosa) dramatically improved model fit (P <.0001 ANOVA f-test), confirming the difference of intracellular fitness associated with ROSA-like insertion.”

In an interview with Infectious Disease Advisor, Dr Rasigade said, “[Our] colleagues from Nîmes have been working recently on the importance of iron uptake dysregulation in strains harboring the phage, [however], their results are not published yet.”

When asked about the implications of this research for immunologists and infectious disease physicians, Dr Rasigade said, “This is the first description of an easily detectable (via PCR) feature of S aureus associated with favorable outcome. Our current hypothesis, to be tested in clinical trials, is that antimicrobial chemotherapy might be avoided for phage-positive strains; in the case where physicians wonder whether to eradicate S aureus from a colonized chronic wound, the presence of the phage would argue against chemotherapy. This might contribute to spare important antimicrobial agents.”

Dr Rasigade and colleagues concluded that these results suggest that colonization-associated phages may prevent the invasive transition of S aureus via inhibiting intracellular growth, particularly in cases of diabetic osteoymelitis. Researchers noted that this “supports our previous proposition that DFU patients colonized with ROSA-like-positive strains …would probably not benefit from S aureus eradication.”

Reference

1. Rasigade JP, Dunyach-Rémy C, Sapin A, et al. A prophage in diabetic foot ulcer-colonizing Staphylococcus aureus impairs invasiveness by limiting intracellular growth. J Infect Dis. 2016 Sep 16. doi: 10.1093/infdis/jiw432. [Epub ahead of print]