Permeases of the sap transporter are required for cathelicidin resistance and virulence of Haemophilus ducreyi in humans
| Autor: | Diane M. Janowicz, Sherri D. Rinker, Margaret E. Bauer, Stanley M. Spinola, Barry P. Katz, Kate R. Fortney, Xiaoping Gu, Beth W. Zwickl |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Virulence Factors medicine.medical_treatment Antimicrobial peptides Mutant Virulence Microbial Sensitivity Tests Biology Cathelicidin Microbiology Chancroid Haemophilus ducreyi Young Adult Major Articles and Brief Reports Cathelicidins parasitic diseases Drug Resistance Bacterial medicine Immunology and Allergy Humans Permease Membrane Transport Proteins Transporter Periplasmic space Middle Aged biology.organism_classification Infectious Diseases Human Experimentation Female Gene Deletion Antimicrobial Cationic Peptides |
| Zdroj: | The Journal of infectious diseases. 206(9) |
| ISSN: | 1537-6613 |
| Popis: | Background. Haemophilus ducreyi encounters several classes of antimicrobial peptides (APs) in vivo and utilizes the sensitive-to-antimicrobial-peptides (Sap) transporter as one mechanism of AP resistance. A mutant lacking the periplasmic solute–binding component, SapA, was somewhat more sensitive to the cathelicidin LL-37 than the parent strain and was partially attenuated for virulence. The partial attenuation led us to question whether the transporter is fully abrogated in the sapA mutant. Methods. We generated a nonpolar sapBC mutant, which lacks both inner membrane permeases of the Sap transporter, and tested the mutant for virulence in human volunteers. In vitro, we compared LL-37 resistance phenotypes of the sapBC and sapA mutants. Results. Unlike the sapA mutant, the sapBC mutant was fully attenuated for virulence in human volunteers. In vitro, the sapBC mutant exhibited significantly greater sensitivity than the sapA mutant to killing by LL-37. Similar to the sapA mutant, the sapBC mutant did not affect H. ducreyi’s resistance to human defensins. Conclusions. Compared with the sapA mutant, the sapBC mutant exhibited greater attenuation in vivo, which directly correlated with increased sensitivity to LL-37 in vitro. These results strongly suggest that the SapBC channel retains activity when SapA is removed. |
| Databáze: | OpenAIRE |
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