MSTPublications: October 2018
Acinetobacter baumannii OxyR regulates the transcriptional response to hydrogen peroxide.
Juttukonda LJ, Green ER, Lonergan ZR, Heffern MC, Chang CJ, Skaar EP.
Infect Immun. 2018 Oct 8. pii: IAI.00413-18. doi: 10.1128/IAI.00413-18. [Epub ahead of print]
Acinetobacter baumannii is a Gram-negative opportunistic pathogen that causes diverse infections, including pneumonia, bacteremia, and wound infections. Due to multiple intrinsic and acquired antimicrobial-resistance mechanisms, A. baumannii isolates are commonly multi-drug resistant and infections are notoriously difficult to treat. The World Health Organization recently highlighted carbapenem-resistant A. baumannii as a ‘critical priority’ for the development of new antimicrobials because of the risk to human health posed by this organism. Therefore, it is important to discover mechanisms used by A. baumannii to survive stresses encountered during infection in order to identify new drug targets. In this study, we identified hydrogen peroxide (H2O2) as a stressor produced in the lung during A. baumannii infection using in vivo imaging and defined OxyR as a transcriptional regulator of the H2O2 stress response. Upon exposure to H2O2, A. baumannii differentially transcribes several hundred genes. However, transcriptional upregulation of genes predicted to detoxify hydrogen peroxide is abolished in A. baumannii genetically inactivated for the transcriptional regulator oxyR. Moreover, inactivation of oxyR in both antimicrobial-susceptible and multi-drug-resistant A. baumannii strains impairs growth in the presence of H2O2 OxyR is a direct regulator of katE and ahpF1, which encode the major H2O2-degrading enzymes in A. baumannii, as confirmed through measurement of promoter binding by recombinant OxyR in electromobility shift assays. Finally, an oxyR mutant is less fit than wild-type A. baumannii during infection of the murine lung. This work reveals a mechanism used by this important human pathogen to survive H2O2 stress encountered during infection.
p73 Is Required for Ovarian Follicle Development and Regulates a Gene Network Involved in Cell-to-Cell Adhesion.
Santos Guasch GL, Beeler JS, Marshall CB, Shaver TM, Sheng Q, Johnson KN, Boyd KL, Venters BJ, Cook RS, Pietenpol JA.
iScience. 2018 Sep 25;8:236-249. doi: 10.1016/j.isci.2018.09.018. [Epub ahead of print]
Update on sinus disease in children with cystic fibrosis: advances in treatment modalities, microbiology, and health-related quality-of-life instruments.
Gallant JN, Mitchell MB, Virgin FW.
Curr Opin Otolaryngol Head Neck Surg. 2018 Oct 8. doi: 10.1097/MOO.0000000000000495. [Epub ahead of print]
Structural basis of respiratory syncytial virus subtype-dependent neutralization by an antibody targeting the fusion glycoprotein.
Tian D, Battles MB, Moin SM, Chen M, Modjarrad K, Kumar A, Kanekiyo M, Graepel KW, Taher NM, Hotard AL, Moore ML, Zhao M, Zheng ZZ, Xia NS, McLellan JS, Graham BS.
Nat Commun. 2017 Nov 30;8(1):1877. doi: 10.1038/s41467-017-01858-w.
Clinical and In Vitro Evidence That Left Ventricular Assist Device-Induced von Willebrand Factor Degradation Alters Angiogenesis.
Bartoli CR, Zhang DM, Hennessy-Strahs S, Kang J, Restle DJ, Bermudez C, Atluri P, Acker MA.
Circ Heart Fail. 2018 Sep;11(9):e004638. doi: 10.1161/CIRCHEARTFAILURE.117.004638.
Blood Vessel Epicardial Substance (BVES) in junctional signaling and cancer.
Parang B, Thompson JJ, Williams CS.
Tissue Barriers. 2018 Oct 11:1-12. doi: 10.1080/21688370.2018.1499843. [Epub ahead of print]