Inflammatory properties of antibiotic-treated bacteria

Abstract

Antibiotics have proven to be enormously effective tools in combating infectious diseases. A common roadblock to the effective use of antibiotics is the development of antibiotic resistance. We have recently observed that the very mechanism by which methicillin‐resistant Staphylococcus aureus (MRSA) becomes antibiotic resistant causes the organism to be more inflammatory to innate immune cells. In this review, we offer some thoughts on the ways in which antibiotics have been observed to influence immune responses to bacteria.

Frontline Science: Antibiotic treatment routes Mycobacterium avium to phagolysosomes without triggering proinflammatory cytokine production in human Mϕs

“…Amikacin and clarithromycin inhibit protein synthesis, rifampicin inhibits RNA synthesis, while ethambutol inhibits cell wall synthesis. Furthermore, literature suggests that cell wall inhibitors can elicit inflammatory killing of bacteria due to release of PAMPs 17 . However, we did not observe MyD88 recruitment or increased inflammatory responses by any of the antibiotics per se or subsequent to Mav killing.…”

“…Treatment of Mav lung infections requires a combination of 2–4 antibiotics, including a macrolide (clarithromycin or azithromycin), rifampin or rifabutin, ethambutol, and often an aminoglycoside (amikacin or streptomycin) 15,16 . Antibiotics that inhibit cell wall synthesis (ethambutol) are typically pro‐inflammatory while antibiotics that inhibit the synthesis of protein (macrolides and aminoglycosides) or nucleic acid (rifampin and rifabutin) are less so 17 . We hypothesized that antibiotic treatment would make Mav lose control of the MavC, resulting in fusion with lysosomes or targeting by autophagy, with activation of inflammatory responses as Mav is degraded.…”

Contribution of the Immune Response to Phage Therapy

“…Notably, an important principle of treatment with bacteriostatic antibiotics is that antibiotic control of bacterial proliferation and spread enables bacterial clearance by host immune cells. Furthermore, antibiotic-mediated damage of bacterial cells facilitates phagosomal lysis and release of pathogen-associated molecular patterns (PAMPs), which enhance bacterial clearance by activating the innate immune system (3)(4)(5)(6). In cases of high bacterial burden, excess release of high amounts of endotoxin (i.e., LPS and other PAMPs) following administration of the antibiotic promotes a systemic inflammatory reaction that can require medical intervention (7).…”

Predatory bacteria as living antibiotics – where are we now?

“…During the predatory lifecycle the prey cell is killed in a short time (<30 min) [40] and therefore the prey would have to express means of defence quickly enough to resist predation, something not yet seen [41]. Unlike some antibiotics, which can cause a cascade of events that lead to bacterial autolysis and release of inflammatory molecules [42], B. bacteriovorus predation does not result in the initial lysis of the prey, as the prey contents are consumed from within a stable bdelloplast structure prior to lysis. In addition, there is no single receptor for prey recognition and attachment.…”