The type VI secretion system (T6SS) is a new secretion system that is widely distributed among Gram-negative bacteria. The core component hemolysin-coregulated protein (Hcp) can be used as both its structural protein and secretory protein or chaperone protein. Studies on Hcp are important to elucidate the overall virulence mechanism of T6SS. Salmonella typhimurium is an important foodborne pathogen. There are three copies of hcp genes identified in S. Typhimurium 14028s. This study aimed to characterize the functions of the three Hcp family proteins and to elucidate the interactions among them. The hcp gene deletion mutants were constructed by λ Red-based recombination system. Effects of hcp mutation on the pathogenicity of 14028s were studied by bacterial competition assays, Dictyostelium discoideum assays and mouse model. The three Hcp family proteins were found to play different roles. Hcp1 can affect the transcription of rpoS and type 2 flagellar gene and influence the motility of 14028s. It is also involved in the intracellular survival of 14028s in Dictyostelium discoideum; Hcp2 is involved in the early proliferative capacity of 14028s in mice and can prevent its excessive proliferation; Hcp3 did not show direct functions in these assays. Hcp1 can interact with Hcp2 and Hcp3. Deletion of one hcp gene can result in a transcription level variation in the other two hcp genes. Our findings elucidated the functions of the three Hcp family proteins in S.Typhimurium and illustrated that there are interactions between different Hcp proteins. This study will be helpful to fully understand how T6SS actions in an organism.

Acinetobacter baumannii is one of the main causes of nosocomial infections. Increasing numbers of multidrug-resistant Acinetobacter baumannii cases have been reported in recent years, but its antibiotic resistance mechanism remains unclear. We studied 9 multidrug-resistant (MDR) and 10 drug-susceptible Acinetobacter baumannii clinical isolates using Label free, TMT labeling approach and glycoproteomics analysis to identify proteins related to drug resistance. Our results showed that 164 proteins exhibited different expressions between MDR and drug-susceptible isolates. These differential proteins can be classified into six groups: a. proteins related to antibiotic resistance, b. membrane proteins, membrane transporters and proteins related to membrane formation, c. Stress response-related proteins, d. proteins related to gene expression and protein translation, e. metabolism-related proteins, f. proteins with unknown function or other functions containing biofilm formation and virulence. In addition, we verified seven proteins at the transcription level in eight clinical isolates by using quantitative RT-PCR. Results showed that four of the selected proteins have positive correlations with the protein level. This study provided an insight into the mechanism of antibiotic resistance of multidrug-resistant Acinetobacter baumannii.

Intestinal mycobiome dysbiosis plays an important role in the advancement of HIV- and HCV-infected patients. Co-infection with HCV is an important risk factor for exacerbating immune activation in HIV-infected patients, and gut fungal microbial dysbiosis plays an important role. However, no systematic study has been conducted on the intestinal fungal microbiome of HIV/HCV co-infected patients to date. Patients infected with HIV and HCV, either alone or in combination, and healthy volunteers were included. Stool samples were collected for fungal ITS sequencing and for further mycobiome statistical analysis. We found that the abundance of fungal species significantly decreased in the HIV/HCV co-infection group compared to in the healthy control group, while no significant differences were found in the mono-infection groups. Low-CD4 + T-cell patients in the HIV group and high-ALT-level patients in the HCV group were discovered to have a more chaotic fungal community. Furthermore, the opportunistic pathogenic fungal profiles and fungal inter-correlations in the co-infection group became less characteristic but more complicated than those in the mono-infection groups. Intestinal fungal dysregulation occurs in HIV- and HCV-infected patients, and this dysregulation is further complicated in HIV/HCV co-infected patients.