Abstract
BackgroundSpecific antibodies mediate humoral and cellular protection against invading pathogens such as Streptococcus pneumoniae by activating complement mediated immunity, promoting phagocytosis and stimulating bacterial clearance. The emergence of pneumococcal strains with high levels of antibiotic resistance is of great concern worldwide and a serious threat for public health.Methodology/Principal FindingsFlow cytometry was used to determine whether complement-mediated immunity against three antibiotic-resistant S. pneumoniae clinical isolates is enhanced in the presence of sub-inhibitory concentrations of cefditoren and ceftriaxone. The binding of acute phase proteins such as C-reactive protein and serum amyloid P component, and of complement component C1q, to pneumococci was enhanced in the presence of serum plus either of these antibiotics. Both antibiotics therefore trigger the activation of the classical complement pathway against S. pneumoniae. C3b deposition was also increased in the presence of specific anti-pneumococcal antibodies and sub-inhibitory concentrations of cefditoren and ceftriaxone confirming that the presence of these antibiotics enhances complement-mediated immunity to S. pneumoniae.Conclusions/SignificanceUsing cefditoren and ceftriaxone to promote the binding of acute phase proteins and C1q to pneumococci, and to increase C3b deposition, when anti-pneumococcal antibodies are present, might help reduce the impact of antibiotic resistance in S. pneumoniae infections.
Highlights
Streptococcus pneumoniae, the pneumococcus, is the leading bacterial cause of community-acquired pneumonia, bacteremia and meningitis, especially among young children and older adults [1]
With both antibiotics, the binding of human C-reactive protein (CRP) and mouse serum amyloid P component (SAP) was significantly increased (Fig. 1). These results suggest that recognition of antibiotic-resistant S. pneumoniae strains by acute phase proteins such as CRP and SAP is enhanced when bacteria are exposed to these antibiotics
Bacteria incubated with human or mouse sera supplemented with 0.5 minimum inhibitory concentrations (MICs) and 0.25 MIC of either CDN or CRO showed greater levels of C1q bound to the bacterial surface than those incubated in serum alone (Fig. 2)
Summary
Streptococcus pneumoniae, the pneumococcus, is the leading bacterial cause of community-acquired pneumonia, bacteremia and meningitis, especially among young children and older adults [1]. Invasive pneumococcal disease (IPD) is associated with high morbidity and mortality, and may be fatal despite appropriate antibiotic treatment. The emergence of strains for which the minimum inhibitory concentrations (MICs) are high, complicates the success of the antibiotic treatment and poses a serious threat worldwide [2]. Activation of the classical pathway is essential in the host immune response to S. pneumoniae; it is the most important route for complement activation against this pathogen in mice and humans [6,7]. Specific antibodies mediate humoral and cellular protection against invading pathogens such as Streptococcus pneumoniae by activating complement mediated immunity, promoting phagocytosis and stimulating bacterial clearance. The emergence of pneumococcal strains with high levels of antibiotic resistance is of great concern worldwide and a serious threat for public health
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