Macrolides and β-lactam antibiotics enhance C3b deposition on the surface of multidrug-resistant Streptococcus pneumoniae strains by a LytA autolysin-dependent mechanism.
The emergence of Streptococcus pneumoniae strains displaying high levels of multidrug resistance is of great concern worldwide and a serious threat for the outcome of the infection. Modifications of the bacterial envelope by antibiotics may assist the recognition and clearance of the pathogen by the host immune system. Recognition of S. pneumoniae resistant strains by the complement component C3b was increased in the presence of specific anti-pneumococcal antibodies and subinhibitory concentrations of different macrolides and β-lactam antibiotics for all the strains investigated. However, C3b levels were unchanged in the presence of serum containing specific antibodies and sub-MICs of levofloxacin. To investigate whether LytA, the main cell wall hydrolase of S. pneumoniae, might be involved in this process, lytA-deficient mutants were constructed. In the presence of antibiotics, loss of LytA was not associated with enhanced C3b deposition on the pneumococcal surface, which confirms the importance of LytA in this interaction. The results of this study offer new insights into the development of novel therapeutic strategies using certain antibiotics by increasing the efficacy of the host immune response to efficiently recognize pneumococcal resistant strains.
Centro de Investigaciones Biológicas (CSIC) and CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
Elisa
E
Ramos-Sevillano
Cinthya
C
Rodríguez-Sosa
Roberto
R
Díez-Martínez
María-José
MJ
Giménez
Eduardo
E
Olmedillas
Pedro
P
García
Ernesto
E
García
Lorenzo
L
Aguilar
Jose
J
Yuste
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002473:Cell Wall / Q000187:drug effects / Q000201:enzymology; D003179:Complement C3b / Q000276:immunology / Q000494:pharmacology*; D003470:Culture Media; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects / Q000235:genetics; D007106:Immune Sera / Q000737:chemistry / Q000276:immunology; D018942:Macrolides / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000235:genetics* / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D047090:beta-Lactams / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D003470:Culture Media; D007106:Immune Sera; D018942:Macrolides; D047090:beta-Lactams; D003179:Complement C3b; D009238:N-Acetylmuramoyl-L-alanine Amidase