Interaction of Antibiotics with Innate Host Defense Factors against Salmonella enterica Serotype Newport

Abstract

It is becoming increasingly understood that the current paradigms of in vitro antimicrobial susceptibility testing may have significant shortcomings in predicting activity in vivo. This study evaluated the activity of several antibiotics alone and in combination against clinical isolates of Salmonella enterica serotype Newport (meningitis case) utilizing both conventional and physiological media. In addition, the interactions of these antibiotics with components of the innate immune system were evaluated. Azithromycin, which has performed quite well clinically despite high MICs in conventional media, was shown to be more active in physiological media and to enhance innate immune system killing. Alternatively, chloramphenicol did not show enhanced immune system killing, paralleling its inferior clinical performance to other antibiotics that have been used to treat Salmonella meningitis. These findings are important additions to the building understanding of current in vitro antimicrobial assay limitations that hopefully will amount to future improvements in these assays to better predict clinical efficacy and activity in vivo.

The Mechanisms of Action of Cationic Antimicrobial Peptides Refined by Novel Concepts from Biophysical Investigations

“…Synergistic enhancement of antimicrobial activities has been described (McCafferty et al 1999;Acar 2000) and includes mixtures of peptides with conventional antibiotics (Chou et al 2016;Bolosov et al 2017;Kim et al 2017;Payne et al 2017;Rank et al 2017;Sakoulas et al 2017) or different peptides such as dermaseptins, bacteriocins (Mor et al 1994;McCafferty et al 1999), magainin 2 and PGLa (Vaz Gomes et al 1993), or magainin and the cyclic β-sheet tachyplesin I sequence (Kobayashi et al 2001). Here we will shortly summarize findings made with magainin 2 and PGLa which have recently been reviewed in more detail (Marquette and Bechinger 2018).…”

Thinking Outside the Box—Novel Antibacterials To Tackle the Resistance Crisis

“…All of these components modulate various pathways and are mainly causative for the altered in vivo efficiency of antibiotics. [69,[71][72][73][74] Efforts were made to mimic in vivo conditions during in vitro AST to account for this contextual antibiotic susceptibility.Astraightforward and very effective approach is the substitution of common rich laboratory medium with minimal medium. [75,76] Ar ecent study by Ersoy et al revealed that the antibiotic susceptibility of various clinical isolates strongly depends on the medium used for in vitro cultivation.…”

Human antimicrobial peptide, LL-37, induces non-inheritable reduced susceptibility to vancomycin inStaphylococcus aureus

“…The lack of predictive value is partly attributed to the fact that the growth media in which the susceptibility tests are conducted, do not sufficiently represent the in vivo environment. Several factors, such as nutrient availability, oxygen level, pH and presence of innate immune components, have been identified to affect antibiotic susceptibility in both Gram-positive and –negative species 22–25 . Here we show that the presence of the antimicrobial peptide LL-37 of the innate immune response antagonizes the activity of vancomycin against S. aureus in vitro .…”