Acinetobacter baumannii Secretes Cytotoxic Outer Membrane Protein A via Outer Membrane Vesicles

Acinetobacter baumannii is an important nosocomial pathogen that causes a high morbidity and mortality rate in infected patients, but pathogenic mechanisms of this microorganism regarding the secretion and delivery of virulence factors to host cells have not been characterized. Gram-negative bacteria naturally secrete outer membrane vesicles (OMVs) that play a role in the delivery of virulence factors to host cells. A. baumannii has been shown to secrete OMVs when cultured in vitro, but the role of OMVs in A. baumannii pathogenesis is not well elucidated. In the present study, we evaluated the secretion and delivery of virulence factors of A. baumannii to host cells via the OMVs and assessed the cytotoxic activity of outer membrane protein A (AbOmpA) packaged in the OMVs. A. baumannii ATCC 19606T secreted OMVs during in vivo infection as well as in vitro cultures. Potential virulence factors, including AbOmpA and tissue-degrading enzymes, were associated with A. baumannii OMVs. A. baumannii OMVs interacted with lipid rafts in the plasma membranes and then delivered virulence factors to host cells. The OMVs from A. baumannii ATCC 19606T induced apoptosis of host cells, whereas this effect was not detected in the OMVs from the ΔompA mutant, thereby reflecting AbOmpA-dependent host cell death. The N-terminal region of AbOmpA22-170 was responsible for host cell death. In conclusion, the OMV-mediated delivery of virulence factors to host cells may well contribute to pathogenesis during A. baumannii infection

Chapter 12 - Antibiotics in the management of tuberculosis and cancer

Drugs that were formerly thought to be life-saving miracles are now rendered useless due to pathogen's defense mechanisms. It is more difficult to fight or cure the infectious disease and to develop new antibiotics due to increase in antibiotic resistance. Mycobacterium tuberculosis is one of the world's most deadly infections and causes of mortality. Recent advances in gene therapy, genetic engineering, and last but not least, immunobiology, establish a reasonable foundation for the research and development of more effective tuberculosis vaccines. Cancer is the uncontrolled proliferation of cells in our bodies that might result in death. Normal cells are typically invaded and destroyed by cancer cells. Due to the complicated nature of cancer, it is necessary to analyze at molecular level, and we hope biotechnologists will develop fast and promising way of more techniques and discovery items in order to decrease the cause of death and to limit suffering percentage of cancerous patients, increasing the drug efficacy, selectivity, and mode of action. Because of advancements in screening, targeted and immunological therapy, big data, computational techniques, and major new knowledge of cancer biology, many diseases could be prevented, detected, diagnosed, and treated. In order to combat the global problem of antibiotic resistance, fundamental research and biotechnology are critical. The widespread adoption of these strategies will be critical in the creation of novel antibiotics for the treatment and prevention of tuberculosis and cancer

Staphylococcus aureus produces membrane-derived vesicles that induce host cell death.

Gram-negative bacteria produce outer membrane vesicles that play a role in the delivery of virulence factors to host cells. However, little is known about the membrane-derived vesicles (MVs) produced by gram-positive bacteria. The present study examined the production of MVs from Staphylococcus aureus and investigated the delivery of MVs to host cells and subsequent cytotoxicity. Four S. aureus strains tested, two type strains and two clinical isolates, produced spherical nanovesicles during in vitro culture. MVs were also produced during in vivo infection of a clinical S. aureus isolate in a mouse pneumonia model. Proteomic analysis showed that 143 different proteins were identified in the S. aureus-derived MVs. S. aureus MVs were interacted with the plasma membrane of host cells via a cholesterol-rich membrane microdomain and then delivered their component protein A to host cells within 30 min. Intact S. aureus MVs induced apoptosis of HEp-2 cells in a dose-dependent manner, whereas lysed MVs neither delivered their component into the cytosol of host cells nor induced cytotoxicity. In conclusion, this study is the first report that S. aureus MVs are an important vehicle for delivery of bacterial effector molecules to host cells