Pseudomonas aeruginosa uses a complex type III secretion system to inject the toxins ExoS, ExoT, ExoU, and ExoY into the cytosol of target eukaryotic cells. This system is regulated by the exoenzyme S regulon and includes the transcriptional activator ExsA. Of the four toxins, ExoU is characterized as the major virulence factor responsible for alveolar epithelial injury in patients with P. aeruginosa pneumonia. Virulent strains of P. aeruginosa possess the exoU gene, whereas non-virulent strains lack this particular gene. The mechanism of virulence for the exoU ⁺ genotype relies on the presence of a pathogenic gene cluster (PAPI-2) encoding exoU and its chaperone, spcU. The ExoU toxin has a patatin-like phospholipase domain in its N-terminal, exhibits phospholipase A₂ activity, and requires a eukaryotic cell factor for activation. The C-terminal of ExoU has a ubiquitinylation mechanism of activation. This probably induces a structural change in enzymatic active sites required for phospholipase A₂ activity. In P. aeruginosa clinical isolates, the exoU ⁺ genotype correlates with a fluoroquinolone resistance phenotype. Additionally, poor clinical outcomes have been observed in patients with pneumonia caused by exoU ⁺ -fluoroquinolone-resistant isolates. Therefore, the potential exists to improve clinical outcomes in patients with P. aeruginosa pneumonia by identifying virulent and antimicrobial drug-resistant strains through exoU genotyping or ExoU protein phenotyping or both.

Staphylococcus aureusis the primary cause of bacteremia, and methicillin-resistantS.aureusbacteremia is associated with a high mortality rate. Methicillin-resistantS.aureusclones are widespread worldwide, and molecular epidemiological studies are important. Therefore, this study aimed to determine the characteristics of patients who died due to methicillin-resistantS.aureusbacteremia and microbiological characteristics of methicillin-resistantS.aureusstrains in a tertiary teaching hospital. This single-center, retrospective study included patients with methicillin-resistantS.aureusisolated from blood bacterial culture performed at Kyoto Prefectural University of Medicine Hospital, from October 2016 to May 2019. The data analyzed included patient background, clinical strain characteristics, and molecular epidemiology. Of 41 patients with methicillin-resistantS.aureusbacteremia (median age, 60 [28–70] years; 24 (59%) were men), and 7 (17%) died due to methicillin-resistantS.aureusbacteremia. The median age of those who died in the methicillin-resistantS.aureusbacteremia group was predominantly higher than that of those in the alive group (p = 0.03). The most common cause of methicillin-resistantS.aureusbacteremia was endovascular devices, which occurred in 20 (49%), 18 (53%), and 2 (29%) patients in the total, alive, and died groups, respectively. Bacteriological characteristics showed that type IV Staphylococcal Cassette Chromosomemecgenotype was most frequently detected in the total (n = 34 [83%]), alive (n = 29 [85%]), and died (n = 5 [71%]) groups. In the molecular cluster analysis, CC8, ST8, staphylococcal Cassette Chromosomemectype IV, and community-acquired-methicillin-resistantS.aureusformed the largest groups. The diversity of methicillin-resistantS.aureusclones is evident, and it is possible that clones with new virulence factors may still emerge. In the future, it will be crucial to monitor the epidemiological trends of methicillin-resistantS.aureusto respond quickly to changes in pathogenic and clonal factors, to clarify the gene expression network by identifying old and new virulence factors.

Introduction: We report a case of COVID-19 with Legionella co-infection that was treated successfully. Case report: A 73-year-old man presented to the hospital with symptoms of fatigue that continued for the next 5 days. The patient was receiving docetaxel and prednisolone chemotherapy for prostate cancer. Laboratory findings on admission showed positive urine Legionella antigen test and SARS-CoV-2 test. He was administered antiviral and antibacterial agents, and a corticosteroid. Pneumonia exacerbated on day 2 of hospitalization. The patient underwent tracheal intubation and began receiving multidisciplinary care. On day 8 of hospitalization, his oxygenation improved, and the patient was extubated. He discharged on day 27 of hospitalization. Conclusions: The patient had a favorable outcome with early diagnosis and early treatment of both diseases. Patients with severe COVID-19 disease need to be evaluated for co-infection. Further, early diagnosis and early treatment of the microbial bacteria causing the co-infection are important.

An effective vaccine against Pseudomonas aeruginosa would benefit people susceptible to severe infection. Vaccination targeting V antigen (PcrV) of the P. aeruginosa type III secretion system is a potential prophylactic strategy for reducing P. aeruginosa-induced acute lung injury and acute mortality. We created a recombinant protein (designated POmT) comprising three antigens: full-length PcrV (PcrV_#1-#294), the outer membrane domain (#190-342) of OprF (OprF_#190-#342), and a non-catalytic mutant of the carboxyl domain (#406-613) of exotoxin A (mToxA_{#406-#613(E553Δ)}). In the combination of PcrV and OprF, mToxA, the efficacy of POmT was compared with that of single-antigen vaccines, two-antigen mixed vaccines, and a three-antigen mixed vaccine in a murine model of P. aeruginosa pneumonia. As a result, the 24 h-survival rates were 79%, 78%, 21%, 7%, and 36% in the POmT, PcrV, OprF, mTox, and alum-alone groups, respectively. Significant improvement in acute lung injury and reduction in acute mortality within 24 h after infection was observed in the POmT and PcrV groups than in the other groups. Overall, the POmT vaccine exhibited efficacy comparable to that of the PcrV vaccine. The future goal is to prove the efficacy of the POmT vaccine against various P. aeruginosa strains.