Anti-capsular activity of CuO nanoparticles against Acinetobacter baumannii produce efflux pump.

Copper oxide nanoparticles are modern kinds of antimicrobials, which may get a lot of interest in the clinical application. This study aimed to detect the anti-capsular activity of CuO nanoparticles against Acinetobacter baumannii produce efflux pump. Thirty-four different clinical A. baumannii isolates were collected and identified by the phenotypic and genetic methods by the recA gene as housekeeping. Antibiotic sensitivity and biofilm-forming ability, capsular formation were carried out. The effect of CuO nanoparticles on capsular isolates was detected, the synergistic effects of a combination CuO nanoparticles and gentamicin against A. baumannii were determined by micro broth checkerboard method, and the effect of CuO nanoparticles on the expression of ptk, espA and mexX genes was analyzed. Results demonstrated that CuO nanoparticles with gentamicin revealed a synergistic effect. Gene expression results show reducing the expression of these capsular genes by CuO nanoparticles is major conduct over reducing A. baumannii capsular action. Furthermore, results proved that there was a relationship between the capsule-forming ability and the absence of biofilm-forming ability. As bacterial isolates which were negative biofilm formation were positive in capsule formation and vice versa. In conclusion, CuO nanoparticles have the potential to be used as an anti-capsular agent against A. baumannii, and their combination with gentamicin can enhance their antimicrobial effect. The study also suggests that the absence of biofilm formation may be associated with the presence of capsule formation in A. baumannii. These findings provide a basis for further research on the use of CuO nanoparticles as a novel antimicrobial agent against A. baumannii and other bacterial pathogens, also to investigate the potential of CuO nanoparticles to inhibit the production of efflux pumps in A. baumannii, which are a major mechanism of antibiotic resistance.

Thirteen-Valent Pneumococcal Conjugate Vaccine-Induced Immunoglobulin G (IgG) Responses in Serum Associated With Serotype-Specific IgG in the Lung.

Pneumococcal conjugate vaccine (PCV) efficacy is lower for noninvasive pneumonia than invasive disease. In this study, participants were immunized with 13-valent PCV (PCV13) or hepatitis A vaccine (control). Bronchoalveolar lavage samples were taken between 2 and 6 months and serum at 4 and 7 weeks postvaccination. In the lung, anti-capsular immunoglobulin G (IgG) levels were higher in the PCV13 group compared to controls for all serotypes, except 3 and 6B. Systemically, IgG levels were elevated in the PCV13 group at 4 weeks for all serotypes, except serotype 3. IgG in bronchoalveolar lavage and serum positively correlated for nearly all serotypes. PCV13 shows poor immunogenicity to serotype 3, implying lack of protective efficacy. Clinical Trials Registration. ISRCTN 45340436.

Long-term immune responses and comparative effectiveness of one or two doses of 7-valent pneumococcal conjugate vaccine (PCV7) in HIV-positive adults in the era of combination antiretroviral therapy.

INTRODUCTION: HIV infection impairs maintenance of immunological memory, yet few studies of HIV-positive adults receiving 7-valent pneumococcal conjugate vaccine (PCV7) have followed them beyond the first year. We determined and compared the durability of serological responses and the clinical outcomes of HIV-positive adults annually for five years following vaccination with one or two doses of PCV7. METHODS: In this non-randomized clinical trial, 221 pneumococcal vaccine-naïve HIV-positive adults receiving one (n = 109) or two doses four weeks apart (n = 112) of PCV7 between 2008 and 2010 were longitudinally followed for evaluation of significant serological response and for episodes of pneumonia and invasive pneumococcal disease. RESULTS: At the time of vaccination, the two groups were well matched for age, risk factors, combination antiretroviral therapy (cART) coverage, CD4 count and plasma HIV RNA load (PVL). At the end of five years, the CD4 counts for the one- and two-dose groups had increased from 407 and 406 to 550 and 592 cells/µL, respectively, and 82.4 and 81.6% of the participants had fully suppressed PVL. Significant immune responses to ≥ 2 serotypes persisted for 67.9 vs 78.6%, 64.2 vs 71.4%, 66.1 vs 71.4%, 57.8 vs 69.6% in the second, third, fourth and fifth years after one and two doses of PCV7 in the intention-to-treat analysis, respectively. In multivariate analysis, immunization with two doses of PCV7 (odds ratio (OR) 1.71, 95% confidence interval (CI) 1.10 to 2.65, p = 0.016), concurrent cART (OR 2.16, 95% CI 1.16 to 4.00, p = 0.015) and CD4 proliferation (OR 1.12, 95% CI 1.01 to 1.27, p = 0.031) were predictive of persistent serological responses in the fifth year. Only one patient in the one-dose group had documented pneumococcal pneumonia (non-bacteraemic) and none had invasive pneumococcal disease in the 6.5 years of follow-up. CONCLUSIONS: One or two doses of PCV7 achieve durable seroprotective responses in HIV-treated participants; however, two doses may be more robust than one dose in a larger study population or in real-world populations with less cART coverage.

Capsular polysaccharides are an important immune evasion mechanism for Staphylococcus aureus.

Staphylococcus aureus can cause severe life threatening invasive diseases. The principal immune effector mechanism by which humans are protected from Gram positive bacteria such as S. aureus is antigen specific antibody- and complement-dependent opsonophagocytosis. This process can be measured in vitro using the opsonophagocytic antibody assay (OPA), which is a complex assay composed of live S. aureus bacteria, a complement source, phagocytic effector cells such as differentiated HL-60 cells, and test serum. In this report, we investigated the impact on the OPA of S. aureus surface antigens capsular polysaccharides (CP) and protein A (SpA). We demonstrated that higher CP expression renders bacteria more resistant to non-specific opsonophagocytic killing than increased SpA expression, suggesting that the expression of capsular polysaccharides may be the more important immune evasion strategy for S. aureus. Bacteria that were not fully encapsulated were highly susceptible to non-specific killing in the assay in the absence of immune serum. This non-specific killing was prevented by growing the bacteria under conditions that increased capsular polysaccharide levels on the surface of the bacteria. In contrast, the level of SpA expression had no detectable effect on non-specific killing in OPA. Using anti-CP antibodies we demonstrated type-specific killing in OPA of both MRSA and MSSA clinical isolates. SpA expression on the cell surface did not interfere with OPA activity, providing evidence that despite the role of SpA in sequestering antibodies by their Fc region, killing is easily accomplished in the presence of high titered anti-capsular polysaccharide antibodies. This highlights the role of CP as an important immune evasion mechanism and supports the inclusion of capsular polysaccharide antigens in the formulation of multi-component prophylactic vaccines against S. aureus.