Assessing bactericidal dynamics of persister-manifested clinical isolates in the presence of macrophages and antibiotics

Abstract

Antibiotics are often depicted to reduce bacterial load for immuno-clearance. Recurring infections can be caused by bacteria persisters that survived antibiotic treatment. It is unclear how the host immunity manages infection by persister-manifested strains during antibiotic treatment. Differentiated THP-1 macrophages were exposed to persister-manifested clinical isolates at various multiplicities-of-infection (MOI), in the presence or absence of meropenem. Across all MOIs, meropenem did not greatly reduce the intracellular bacterial load nor eradicate all extra-macrophagic non-persister bacteria. Bactericidal effects on extracellular bacteria vary for each strain after meropenem treatment in mildly infected macrophages. In severely infected macrophages, extra-macrophagic bacteria of all isolates decreases in numbers followed by a bacteriostatic-like effect. Our findings contradict the common notion that antibiotics generally reduce the bacterial load for immune clearance. Our study suggests that the bactericidal effects of meropenem differs with host presence and can be dependent on bacterial load.