Abstract
Biofilms of S. aureus accumulate cells resistant to the antibiotic rifampicin. We show here that the accumulation of rifampicin resistant mutants (RifR) in biofilms is not equable but rather is a local event, suggesting that the growth of a few locally emerged mutants is responsible for this. Competition assays demonstrated that, compared to wild-type bacteria, the isolated RifR mutants have a growth advantage in biofilms, but not in planktonic culture. To gain insight into the mechanism of the growth advantage, we tested the involvement of the two-component systems (TCS) that sense and respond to environmental changes. We found that a deletion of SrrAB or NreBC has a drastic effect on the growth advantage of RifR mutants, suggesting the importance of oxygen/respiration responses. All six of the RifR isolates tested showed increased resistance to at least one of the common stresses found in the biofilm environment (i.e., oxidative, nitric acid, and organic acid stress). The RifR mutants also had a growth advantage in a biofilm flow model, which highlights the physiological relevance of our findings.
Highlights
Staphylococcus aureus is an opportunistic human pathogen responsible for diverse infectious diseases (Lowy, 1998; Wertheim et al, 2005)
We found that spontaneous rifampicin resistant mutants had a growth advantage in the biofilm environment but not in liquid cultures
We investigated the nature of rifampicin resistant cells (RifR) that accumulated in S. aureus biofilms using a plasma coated cellulose disk biofilm model as previously described (Ryder et al, 2012)
Summary
Staphylococcus aureus is an opportunistic human pathogen responsible for diverse infectious diseases (Lowy, 1998; Wertheim et al, 2005). S. aureus biofilm-associated infections are especially difficult to treat by antibiotics since their penetration into the structure and access to the bacterial cells is inhibited, a series of preventative and treatment strategies have been tested (Suresh et al, 2018). Implanted materials, such as catheters or cannula, often get coated in biomolecules which can play a role in facilitating attachment, and subsequent development of biofilms, of S. aureus (Khatoon et al, 2018). A recent report failed to show a benefit in using rifampicin as an adjunct to standard antibiotic therapy against S. aureus bacteremia (Thwaites et al, 2018), rifampicin is one of the antibiotics that can efficiently penetrate the biofilm of S. aureus (Raad et al, 2007), and the use of rifampicin on biofilm-related infections has long been considered rational
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