Background: The aim of the present study was to undertake a systematic review exploring the relationship between childhood obesity and fecal microorganisms, to answer the following question: “Are Firmicutes and Bacteroidetes a significant risk indicator/factor for obesity in children?” The main search terms were “child” and “obesity” together with “gut microbiota” (PubMed: 2005–2017). The minimal requirements for inclusion were the evaluation of gut microbiota composition and BMI in children between 0 and 13 years of age. Methods: Assessed articles were carefully classified according to a predetermined criterion, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were considered. Seven articles were critically appraised and used as a basis for conclusions. Results: Three studies showed a positive association between Bacteroides fragilis and obesity. In addition, a high value of evidence indicated that a decrease in the Bacteroidetes phylum and in Bacteroides/Prevotella groups was related to high BMI. For the Firmicutes phylum, one high-quality study highlighted that it was positively correlated with weight gain. With regard to Firmicutes species, Clostridium leptum , Eubacterium hallii , and Lactobacillus spp. indicated adipose tissue storage, while Clostridium difficile and the Staphylococcus genus were correlated with low BMI. Despite the fact that only one study did not perform real-time polymerase chain reaction to quantify the microorganisms, its results corroborated those of the studies that did. Conclusions: Changes in Firmicutes and Bacteroidetes phyla/species levels might in fact be significant indicators/factors for childhood obesity. However, given the small number of articles appraising these entire phyla and the heterogeneity among the species assessed, further well-designed studies are required to improve the knowledge.
With the alarming increase of infections caused by pathogenic multidrug-resistant bacteria over the last decades, antimicrobial peptides (AMPs) have been investigated as a potential treatment for those infections, directly through their lytic effect or indirectly, due to their ability to modulate the immune system. There are still concerns regarding the use of such molecules in the treatment of infections, such as cell toxicity and host factors that lead to peptide inhibition. To overcome these limitations, different approaches like peptide modification to reduce toxicity and peptide combinations to improve therapeutic efficacy are being tested. Human defense peptides consist of an important part of the innate immune system, against a myriad of potential aggressors, which have in turn developed different ways to overcome the AMPs microbicidal activities. Since the antimicrobial activity of AMPs vary between Gram-positive and Gram-negative species, so do the bacterial resistance arsenal. This review discusses the mechanisms exploited by Gram-positive bacteria to circumvent killing by antimicrobial peptides. Specifically, the most clinically relevant genera, Streptococcus spp., Staphylococcus spp., Enterococcus spp. and Gram-positive bacilli, have been explored.
2 September 2021 in Infectious Diseases and Therapy
Klebsiella pneumoniae is a bacterium capable of colonizing mucous membranes, causing serious infections. Widespread antibiotic resistance in K. pneumoniae—either through intrinsic mechanisms or via acquisition from different species, especially in hospital environments—limits the therapeutic options against this pathogen, further aggravating the disease burden. To date, there are no vaccines available against K. pneumoniae infection. Although formulations based on capsular polysaccharides have been proposed, the high variability in capsular serotypes limits vaccine coverage. Recombinant vaccines based on surface exposed bacterial antigens are a promising alternative owing to their conservation among different serotypes and accessibility to the immune system. Many vaccine candidates have been proposed, some of which have reached clinical trials. The present review summarizes the current status of K. pneumoniae vaccine development. Different strategies including whole cell vaccines, outer membrane vesicles (OMVs), ribosome, polysaccharide, lipopolysaccharide (LPS), and protein-based formulations are discussed. The contribution of antibody and cell-mediated responses is also presented. In summary, K. pneumoniae vaccines are feasible and a promising strategy to prevent infections and to reduce the antimicrobial resistance burden worldwide.
For reliable results, Reverse Transcription Quantitative real-time Polymerase Chain Reaction (RT-qPCR) analyses depend on stably expressed reference genes for data normalization purposes.Klebsiella pneumoniaeis an opportunistic Gram-negative bacterium that has become a serious threat worldwide. Unfortunately, there is no consensus for an ideal reference gene for RT-qPCR data normalization onK. pneumoniae. In this study, the expression profile of eleven candidate reference genes was assessed inK. pneumoniaecells submitted to various experimental conditions, and the expression stability of these candidate genes was evaluated using statistical algorithms BestKeeper, NormFinder, geNorm, Delta CTand RefFinder. The statistical analyses rankedrecA,rho,proCandrpoDas the most suitable reference genes for accurate RT-qPCR data normalization inK. pneumoniae. The reliability of the proposed reference genes was validated by normalizing the relative expression of iron-regulated genes inK. pneumoniaecells submitted to iron-replete and iron-limited conditions. This work emphasizes that the stable expression of any potential reference candidate gene must be validated in each physiological condition or experimental treatment under study.
Pneumococcal surface protein A (PspA) and PspC are virulence factors that are involved in the adhesion of Streptococcus pneumoniae to epithelial cells and/or evasion from the immune system. Here, the immune responses induced by mucosal vaccines composed of both antigens as recombinant proteins or delivered by Lactobacillus casei were evaluated. None of the PspC vaccines protected mice against an invasive challenge with pneumococcal strain ATCC 6303. On the other hand, protection was observed for immunization with vaccines composed of PspA from clade 5 (PspA5 or L. casei expressing PspA5) through the intranasal route. The protective response was distinguished by a Th1 profile with high levels of immunoglobulin G2a production, efficient complement deposition, release of proinflammatory cytokines, and infiltration of neutrophils. Intranasal immunization with PspA5 elicited the highest level of protection, characterized by increased levels of secretion of interleukin-17 and gamma interferon by lung and spleen cells, respectively, and low levels of tumor necrosis factor alpha in the respiratory tract.
The complement system plays a central role in immune defense against Streptococcus pneumoniae. In order to evade complement attack, pneumococci have evolved a number of mechanisms that limit complement mediated opsonization and subsequent phagocytosis. This review focuses on the strategies employed by pneumococci to circumvent complement mediated immunity, both in vitro and in vivo. At last, since many of the proteins involved in interactions with complement components are vaccine candidates in different stages of validation, we explore the use of these antigens alone or in combination, as potential vaccine approaches that aim at elimination or drastic reduction in the ability of this bacterium to evade complement.