Manca Lab
Research Summary
Dr. Manca’s research has been aimed primarily to study the interaction between the host innate immune cells (monocytes/macrophages) and Mycobacterium tuberculosis or Mycobacterium leprae with special focus on the role that selected cytokines/chemokines play in pathogenesis.
More recently, as a participant of the Antibacterial Resistance Leadership Group (ARLG), she is involved in a series of studies targeting the development of new analytical strategies that can help the evaluation of rapid molecular diagnostics to combat antibiotic resistance.
Tuberculosis: Understanding how the human protective immune response to tuberculosis is regulated has been the focus of several of her studies. Her data have suggested that different clinical isolates of M.tb are differentially able to induce monocyte activation which is associated with disease severity in patients. Certain members of the highly pathogenic W/Beijing family of M. tuberculosis strains produce lipids that interfere with efficient induction of the cytokine-dependent Th1-type protective immune response. In the infected host this failure would result in delayed or impaired protective immunity, leading to more severe disease. Her studies have suggested that the virulence of the W/Beijing strains may in part be attributed to their ability to subvert the host’s protective immune response by suboptimal induction of the cytokine-dependent Th1-type protective immune response while favoring Type I IFN.
Leprosy: is a chronic but treatable infectious disease caused by the intracellular pathogen Mycobacterium leprae. Host immunity to M. leprae determines the clinical outcome of infection, i.e. tuberculoid versus lepromatous disease. Her studies have been focused to better understand the pivotal early molecular events that determine the clinical manifestations of the disease, and how this microorganism interferes with the establishment of an effective host innate immune response.
Antimicrobial Resistance: Antibiotic resistance is increasing in prevalence. Infections with carbapenem-resistant Klebsiella pneumonia (CRKp) strains are associated with high rates of morbidity and mortality, and this incidence is a current national priority (The National Action Plan for Combating Antibiotic-Resistant Bacteria). There is the need for the development and implementation of rapid molecular diagnostics (RMDs) to combat this antibiotic resistance, thereby improving clinical outcomes, and shortening the duration of therapy. She is participating in a series of studies targeting the development of new analytical strategies that can help the evaluation of RMDs.
Relevant Publications
Pandey R, Chen L, Manca C, Jenkins S, Glaser L, Vinnard C, Stone G, Lee J, Mathema B, Nuermberger EL, Bonomo RA, Kreiswirth BN. Dual β-Lactam Combinations Highly Active against Mycobacterium abscessus Complex In Vitro. MBio. 2019.
Evans SR, Tran TTT, Hujer AM, Hill CB, Hujer KM, Mediavilla JR, Manca C, Domitrovic TN, Perez F, Farmer M, Pitzer KM, Wilson BM, Kreiswirth BN, Patel R, Jacobs MR, Chen L, Fowler VG Jr, Chambers HF, Bonomo RA; Antibacterial Resistance Leadership Group (ARLG). Rapid Molecular Diagnostics (RMDs) to Inform Empiric Use of Ceftazidime/Avibactam and Ceftolozane/Tazobactam against Pseudomonas aeruginosa: PRIMERS IV. 2018. Clin Infect Dis.
Manca C., Hill C, Hujer AM, Patel R, Evans SR, Bonomo RA, Kreiswirth BN; Laboratory Center of the Antibacterial Resistance Leadership Group (ARLG). Leadership Group. Leading Antibacterial Laboratory Research by Integrating Conventional and Innovative Approaches: The Laboratory Center of the Antibacterial Resistance Leadership Group. Clin Infect Dis. 2017.
Ferrian, S., Manca, C., Lubbe, S., Conradie, F., Ismail, N., Kaplan, G., Gray, C.M, and Dorothy Fallows. A combination of baseline plasma immune markers can predict therapeutic response in multidrug resistant tuberculosis. PlosOne. 2017.
Evans, SR., Hujer, A.M., Jiang, H., Hill, C.B., Hujer, K.M., Mediavilla, J.R., Manca, C., Domitrovic, T.N., Higgins, P.G., Kreiswirth, B.N., Patel, R., Jacobs, M.R., Chen, L., Sampath, R., Hall, T., Marzan, C., Fowler, V., Jr, Chambers, H., Bonomo, R.A., and The Antibiotic Resistance Leadership Group (ARLG). Informing Antibiotic Treatment Decisions: Evaluating Rapid Molecular Diagnostics (RMDs) to Identify Susceptibility and Resistance to Carbapenems against Acinetobacter spp. PRIMERS–III. J Clin Microbiol. 55(1):134-144. 2017.
Chavda, K., Satlin, M., Chen, L., Manca, C., Jenkins, S., Walsh, T., and Barry Kreiswirth. Evaluation of a Multiplex PCR Assay to Rapidly Detect Enterobacteriaceae with a Broad Range of β-lactamases Directly from Perianal Swabs. Antimicrobial Agent and Chemotherapy. 2016. Oct 21;60(11):6957-6961.
Evans SR, Pennello G, Pantoja-Galicia N, Jiang H, Hujer AM, Hujer KM, Manca C, Hill C, Jacobs MR, Chen L, Patel R, Kreiswirth BN, Bonomo RA; Antibacterial Resistance Leadership Group (ARLG). Benefit-Risk Evaluation for Diagnostics: A Framework (BED-FRAME). Clinical Infectious Diseases. 2016.
Evans SR, Hujer AM, Jiang H, Hujer KM, Hall T, Marzan C, Jacobs MR, Sampath R, Ecker DJ, Manca C, Chavda K, Zhang P, Fernandez H, Chen L, Mediavilla JR, Hill CB, Perez F, Caliendo AM, Fowler VG, Jr., Chambers HF, Kreiswirth BN, and Robert A. Bonomo. Rapid Molecular Diagnostics, Antibiotic Treatment Decisions, and Developing Approaches to Inform Empiric Therapy: PRIMERS I and II. Clinical Infectious Diseases. 62(2):181-9. 2015.
Fallows, D., Peixoto, B., Kaplan, G., and C. Manca. Mycobacterium leprae alters classical activation of human monocytes in vitro. Journal of Inflammation. 13:8. 2016.
Manca, C., Peixoto, B., Malaga, W., Guilhot, C., and G. Kaplan. Modulation of the cytokine response in human monocytes by Mycobacterium leprae phenolic glycolipid-1 (PGL-1). Journal of Interferon and Cytokines Research. 2011.
Sinsimer, D., Fallows, D., Peixoto, B., Krahenbuhl, J., Kaplan, G., and C. Manca. Mycobacterium leprae actively modulates the cytokine response in naïve human monocytes. Infect. Immun. 78(1):293-300, 2010.
Manca, C., Reed, M., Freeman, S., Mathema, B., Kreiswirth, B., Barry 3rd, C.E., and G. Kaplan. Differential monocyte activation underlies strain specific M. tuberculosis pathogenesis. Infec. Immun., 72(9):5511-4, 2004.
Manca, C., Tsenova, L., Bergtold, A., Freeman, S., Tovey, M., Musser, J.M., Barry 3rd, C.E., Freedman, V.H., and G. Kaplan. Virulence of a Mycobacterium tuberculosis clinical isolate in mice is determined by failure to induce Th1 type immunity and is associated with induction of IFN-α/β. Proc Natl Acad Sci U S A. 98(10):5752-7, 2001.
Manca, C., Tsenova, L., Freeman, S., Barczak, A., Tovey, M., Murray, P.J., Barry 3rd, C., and G Kaplan. Hypervirulent M. tuberculosis W/Beijing strains upregulate type I IFNs and increase expression of negative regulators of the Jak/Stat pathway. J. Interferon Cytokine Res. 25(11):694-701, 2005.
Reed, M.B., Domenech, P., Manca, C., Su, H., Barczak, A.K., Kreiswirth, B., Kaplan, G., and C.E. Barry 3rd. A glycolipid of a hypervirulent tuberculosis strain that inhibits the innate immune response. Nature. 431(7004):84-7, 2004.
Manca, C., Tsenova, L., Barry, C.E.3rd, Bergtold, A., Freeman, S., Haslett, P., Musser, J.M., Freedman, V.H., and G. Kaplan. Mycobacterium tuberculosis CDC1551 induces a more vigorous host response in vivo and in vitro, but is not more virulent than other clinical isolates. J. Immunol. 162(11):6740-6, 1999.