title: Acinetobacter baumannii universal stress protein A plays a pivotal role in stress response and is essential for pneumonia and sepsis pathogenesis.
abstract: Acinetobacter baumannii is one of the most significant threats to global public health. This threat is compounded by the fact that A. baumannii is rapidly becoming resistant to all relevant antimicrobials. Identifying key microbial factors through which A. baumannii resists hostile host environment is paramount to the development of novel antimicrobials targeting infections caused by this emerging pathogen. An attractive target could be a molecule that plays a role in the pathogenesis and stress response of A. baumannii. Accordingly, the universal stress protein A (UspA) was chosen to be fully investigated in this study. A platform of A. baumannii constructs, expressing various levels of the uspA gene ranging from zero to thirteen folds of wild-type level, and a recombinant E. coli strain, were employed to investigate the role of UspA in vitro stress and in vivo pathogenesis. The UspA protein plays a significant role in protecting A. baumannii from H(2)O(2), low pH, and the respiratory toxin 2,4-DNP. A. baumannii UspA protein plays an essential role in two of the deadliest types of infection caused by A. baumannii; pneumonia and sepsis. This distinguishes A. baumannii UspA from its closely related homolog, the Staphylococcus aureus Usp2, as well as from the less similar Burkholderia glumae Usps. Heterologous and overexpression experiments suggest that UspA mediates its role via an indirect mechanism. Our study highlights the role of UspA as an important contributor to the A. baumannii stress and virulence machineries, and polishes it as a plausible target for new therapeutics.
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
authors.forename: Noha M
authors.initials: NM
authors.lastname: Elhosseiny
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
authors.forename: Magdy A
authors.initials: MA
authors.lastname: Amin
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
authors.forename: Aymen S
authors.initials: AS
authors.lastname: Yassin
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt. Electronic address: ahmed.s.attia@staff.cu.edu.eg.
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Attia
mesh_terms: D040981:Acinetobacter baumannii / Q000502:physiology*; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018410:Pneumonia, Bacterial / Q000382:microbiology / Q000473:pathology*; D018805:Sepsis / Q000382:microbiology* / Q000473:pathology*; D013312:Stress, Physiological; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D006360:Heat-Shock Proteins; D037521:Virulence Factors; C078564:universal stress protein A, Bacteria
keywords: Acinetobacter baumannii; Pathogenesis; Universal stress protein; Virulence factors