Search

Background The number of patients with skin and soft tissue infections (SSTIs) in the United States appeared to be increasing well into the 21st century. However, no recent data have confirmed this trend. Methods This retrospective, observational cohort study used claims data over 11 years (2010–2020) from Optum's de-identified Clinformatics Data Mart Database. SSTI episodes, complications, and comorbidities were identified using International Classification of Diseases codes. Annual SSTI incidence rates, proportions of recurrent SSTI, SSTI-associated deaths, and total costs were estimated. Results During the study period, 5.4 million patients experienced 9.1 million SSTI episodes, with an incidence of 77.5 (95% confidence interval, 77.4–77.5) per 1000 person-years of observation (PYO). Annual incidence did not change significantly over time. Overall incidence (per 1000 PYO) of SSTI episodes in patients without comorbidities was 32.1 (highest incidence was for previous SSTI [113.5]) versus much higher rates if comorbidities were present. Incidence rates (per 1000 PYO) of chronic ulcers increased over time from 11.3 to 18.2 (P <.0001) and complicated disease from 3.5 to 6.3 (P <.0001). Deaths occurring within 30 days post–SSTI hospitalization rose from 2.6% to 4.6% in 2020. Recurrences occurred in 26.3% of index cases. The mean cost of an SSTI episode was US$3334 (median US$190) and was highest for surgical site infections and chronic ulcers. Conclusions The epidemiology of SSTI in the United States is changing and the disease burden is increasing despite stabilization in overall incidence. These data can inform identification of priority populations who could benefit from targeted interventions. [ABSTRACT FROM AUTHOR]

Skin and soft tissue infections (SSTIs) are the most common diseases caused by Staphylococcus aureus (S. aureus), which can progress to threatening conditions due to recurrences and systemic complications. Staphylococcal protein A (SpA) is an immunomodulator antigen of S. aureus, which allows bacterial evasion from the immune system by interfering with different types of immune responses to pathogen antigens. Immunization with SpA could potentially unmask the pathogen to the immune system, leading to the production of antibodies that can protect from a second encounter with S. aureus, as it occurs in skin infection recurrences. Here, we describe a study in whichmice are immunizedwith a mutated form of SpA mixedwith the Adjuvant System 01 (SpAmut/AS01) before a primary S. aureus skin infection. Although mice are not protected from the infection under these conditions, they are able to mount a broader pathogen-specific functional immune response that results in protection against systemic dissemination of bacteria following an S. aureus second infection (recurrence). We show that this "hidden effect" of SpA can be partially explained by higher functionality of induced anti-SpA antibodies, which promotes better phagocytic activity. Moreover, a broader and stronger humoral response is elicited against several S. aureus antigens that during an infection are masked by SpA activity, which could prevent S. aureus spreading from the skin through the blood. [ABSTRACT FROM AUTHOR]

Analysis of publicly available genomes of Streptococcus pneumoniae has led to the identification of a new genomic element containing genes typical of gram-positive pilus islets (PIs). Here, we demonstrate that this genomic region, herein referred to as PI-2 (consisting of pitA, sipA, pitB, srtG1, and srtG2) codes for a second functional pilus in pneumococcus. Polymerization of the PI-2 pilus requires the backbone protein PitB as well as the sortase SrtG1 and the signal peptidase-like protein SipA. Presence of PI-2 correlates with the genotype as defined by multilocus sequence typing and clonal complex (CC). The PI-2-positive CCs are associated with serotypes 1, 2, 7F, 19A, and 19F, considered to be emerging serotypes in both industrialized and developing countries. Interestingly, strains belonging to CC271 (where sequence type 271 is the predicted founder of the CC) contain both PI-1 and PI-2, as revealed by genome analyses. In these strains both pili are surface exposed and independently assembled. Furthermore, in vitro experiments provide evidence that the pilus encoded by PI-2 of S. pneumoniae is involved in adherence. Thus, pneumococci encode at least two types of pili that play a role in the initial host cell contact to the respiratory tract and are potential antigens for inclusion in a new generation of pneumococcal vaccines.

CagA is a bacterial effector protein of Helicobacter pylori that is translocated via a type IV secretion system into gastric epithelial cells. We previously described that H. pylori require CagA to disrupt the organization and assembly of apical junctions in polarized epithelial cells. In this study, we provide evidence that CagA expression is not only sufficient to disrupt the apical junctions but also perturbs epithelial differentiation. CagA-expressing cells lose apicobasal polarity and cell-cell adhesion, extend migratory pseudopodia, and degrade basement membranes, acquiring an invasive phenotype. Expression of the CagA C-terminal domain, which contains the tyrosine phosphorylated EPIYA motifs, induces pseudopodial activity but is not sufficient to induce cell migration. Conversely, the N terminus targets CagA to the cell-cell junctions. Neither domain is sufficient to disrupt cell adhesion or cell polarity, but coexpressed in trans, the N terminus determines the localization of both polypeptides. We show that CagA induces a morphogenetic program in polarized Madin-Darby canine kidney cells resembling an epithelial-to-mesenchymal transition. We propose that altered cell-cell and cell matrix interactions may serve as an early event in H. pylori-induced carcinogenesis. differentiation | polarity | cell junctions | type IV secretion system | epithelial-to-mesenchymal transition