Generic and Specific Adaptive Responses ofStreptococcus pneumoniaeto Challenge with Three Distinct Antimicrobial Peptides, Bacitracin, LL-37, and Nisin

Abstract

To investigate the response of Streptococcus pneumoniae to three distinct antimicrobial peptides (AMPs), bacitracin, nisin, and LL-37, transcriptome analysis of challenged bacteria was performed. Only a limited number of genes were found to be up-or downregulated in all cases. Several of these common highly induced genes were chosen for further analysis, i.e., SP0385-SP0387 (SP0385-0387 herein), SP0912-0913, SP0785-0787, SP1714-1715, and the blp gene cluster. Deletion of these genes in combination with MIC determinations showed that several putative transporters, i.e., SP0785-0787 and SP0912-0913, were indeed involved in resistance to lincomycin and LL-37 and to bacitracin, nisin, and lincomycin, respectively. Mutation of the blp bacteriocin immunity genes resulted in an increased sensitivity to LL-37. Interestingly, a putative ABC transporter (SP1715) protected against bacitracin and Hoechst 33342 but conferred sensitivity to LL-37. A GntR-like regulator, SP1714, was identified as a negative regulator of itself and two of the putative transporters. In conclusion, we show that resistance to three different AMPs in S. pneumoniae is mediated by several putative ABC transporters, some of which have not been associated with antimicrobial resistance in this organism before. In addition, a GntR-like regulator that regulates two of these transporters was identified. Our findings extend the understanding of defense mechanisms of this important human pathogen against antimicrobial compounds and point toward novel proteins, i.e., putative ABC transporters, which can be used as targets for the development of new antimicrobials.

The Pneumococcal Cell Envelope Stress-Sensing System LiaFSR Is Activated by Murein Hydrolases and Lipid II-Interacting Antibiotics

“…1A) and includes the genes encoding the LiaFSR system (spr0343/44), thereby verifying the positive autoregulatory feedback loop observed for the homologous systems in B. subtilis, L. lactis, S. aureus, and Streptococcus mutans (21,29,43,47). Induction of the liaFSR operon and its downstream genes by bacitracin has also recently been described for the S. pneumoniae strain D39 (28). The three truncated genes directly downstream of liaSR encode N-terminal, central, and C-terminal fragments of a potential DNA alkylation repair enzyme, homologous to AlkD.…”

Variation in Streptococcus pneumoniae susceptibility to human antimicrobial peptides may mediate intraspecific competition

“…Similarly, deletion of choline-binding proteins, such as LytA, increases pneumococcal susceptibility to AMPs [47]. In addition, pneumococcus can alter its gene-expression as a result of exposure to AMPs and can physiologically increase resistance [48]. All but two strains used in this study have different genetic backgrounds as defined by MLST (table 1), and those strains that do share serotype and ST type vary markedly in their response to AMPs.…”

Lantibiotic Resistance

“…Furthermore, expression of sp0912 was induced by up to 13-fold upon treatment with nisin or bacitracin (138) and, more recently, was found to be regulated by a TCS designated Rr01-Hk01 (105).…”