Abstract
The antimicrobial activity of the chemokine CXCL10 against vegetative cells of Bacillus anthracis occurs via both bacterial FtsE/X-dependent and-independent pathways. Previous studies established that the FtsE/X-dependent pathway was mediated through interaction of the N-terminal region(s) of CXCL10 with a functional FtsE/X complex, while the FtsE/X-independent pathway was mediated through the C-terminal α-helix of CXCL10. Both pathways result in cell lysis and death of B. anthracis. In other bacterial species, it has been shown that FtsE/X is involved in cellular elongation though activation of complex-associated peptidoglycan hydrolases. Thus, we hypothesized that the CXCL10-mediated killing of vegetative cells of B. anthracis through the FtsE/X-dependent pathway resulted from the disruption of peptidoglycan processing. Immunofluorescence microscopy studies using fluorescent peptidoglycan probes revealed that incubation of B. anthracis Sterne (parent) strain with CXCL10 or a C-terminal truncated CXCL10 (CTTC) affected peptidoglycan processing and/or incorporation of precursors into the cell wall. B. anthracis ΔftsX or ftsE(K123A/D481N) mutant strains, which lacked a functional FtsE/X complex, exhibited little to no evidence of disruption in peptidoglycan processing by either CXCL10 or CTTC. Additional studies demonstrated that the B. anthracis parent strain exhibited a statistically significant increase in peptidoglycan release in the presence of either CXCL10 or CTTC. While B. anthracis ΔftsX strain showed increased peptidoglycan release in the presence of CXCL10, no increase was observed with CTTC, suggesting that the FtsE/X-independent pathway was responsible for the activity observed with CXCL10. These results indicate that FtsE/X-dependent killing of vegetative cells of B. anthracis results from a loss of cell wall integrity due to disruption of peptidoglycan processing and suggest that FtsE/X may be an important antimicrobial target to study in the search for alternative microbial therapeutics.
Highlights
Chemokines are a large family of proteins that mediate the recruitment of leukocytes during the innate and adaptive immune response (Rossi and Zlotnik, 2000; Zlotnik and Yoshie, 2000, 2012)
Because recombinant human CXCL10 was the most potent against vegetative cells of B. anthracis (Crawford et al, 2009), we focused our attention on the antimicrobial effects of this chemokine
Previous studies with B. anthracis ftsX and ftsE(K123A/D481N) showed that they have about a 30 min lag phase prior to initiation of log phase growth in brain heart infusion (BHI) broth media compared to the parent strain (Crawford et al, 2011; Margulieux et al, 2016)
Summary
Chemokines are a large family of proteins that mediate the recruitment of leukocytes during the innate and adaptive immune response (Rossi and Zlotnik, 2000; Zlotnik and Yoshie, 2000, 2012). A number of chemokines have been shown to have a direct antimicrobial effect against a wide variety of pathogens (Cole et al, 2001; Durr and Peschel, 2002; Yang et al, 2003; Crawford et al, 2009; Nguyen and Vogel, 2012; Yung and Murphy, 2012; Schutte et al, 2016). FtsE/X may be an important bacterial target for development of new antimicrobial strategies (Bugg et al, 2011; Typas et al, 2011)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
