Open Access. Powered by Scholars. Published by Universities.®

Life Sciences Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 4 of 4

Full-Text Articles in Life Sciences

Evaluation Of Il-1 Blockade As A Host-Directed Therapy For Tuberculosis In Mice And Macaques, Caylin G. Winchell, Bibhuti B. Mishra, University Of Massachusetts Medical School, Samantha J. Nelson, Christopher M. Sassetti, Joanne L. Flynn Oct 2019

Evaluation Of Il-1 Blockade As A Host-Directed Therapy For Tuberculosis In Mice And Macaques, Caylin G. Winchell, Bibhuti B. Mishra, University Of Massachusetts Medical School, Samantha J. Nelson, Christopher M. Sassetti, Joanne L. Flynn

University of Massachusetts Medical School Faculty Publications

In 2017, there were over 550,000 estimated new cases of multi-drug/rifampicin resistant tuberculosis (MDR/RR-TB), emphasizing a need for new treatment strategies. Linezolid (LZD) is a potent antibiotic for antibiotic-resistant Gram-positive infections and is an effective treatment for TB. However, extended LZD use can lead to LZD-associated host toxicities, most commonly bone marrow suppression. LZD toxicities may be mediated by IL-1, a pathway important for early immunity during M. tuberculosis infection that later contributes to pathology. We hypothesized LZD efficacy could be enhanced by modulation of IL-1 pathway to reduce BM toxicity and TB associated-inflammation. We used two ...


Chitosan Biosynthesis And Virulence In The Human Fungal Pathogen Cryptococcus Gattii, Woei C. Lam, Rajendra Upadhya, Charles A. Specht, Abigail E. Ragsdale, Camaron R. Hole, Stuart M. Levitz, Jennifer K. Lodge Sep 2019

Chitosan Biosynthesis And Virulence In The Human Fungal Pathogen Cryptococcus Gattii, Woei C. Lam, Rajendra Upadhya, Charles A. Specht, Abigail E. Ragsdale, Camaron R. Hole, Stuart M. Levitz, Jennifer K. Lodge

University of Massachusetts Medical School Faculty Publications

Cryptococcus gattii R265 is a hyper-virulent fungal strain responsible for the major outbreak of cryptococcosis in Vancouver Island of British Columbia in 1999. It differs significantly from C. neoformans in its natural environment, its preferred site in the mammalian host, and in the nature and mode of pathogenesis. Our previous studies in C. neoformans have shown that the presence of chitosan, the deacetylated form of chitin, in the cell wall attenuates inflammatory responses in the host, while its absence induces robust immune responses, which in turn facilitate clearance of the fungus and induces a protective response. The results of the ...


The Aminoalkylindole, Bml-190, Negatively Regulates Chitosan Synthesis Via The Camp/Pka1 Pathway In Cryptococcus Neoformans, Brian T. Maybruck, Woei C. Lam, Charles A. Specht, Ma Xenia G. Ilagan, Maureen J. Donlin, Jennifer K. Lodge Aug 2019

The Aminoalkylindole, Bml-190, Negatively Regulates Chitosan Synthesis Via The Camp/Pka1 Pathway In Cryptococcus Neoformans, Brian T. Maybruck, Woei C. Lam, Charles A. Specht, Ma Xenia G. Ilagan, Maureen J. Donlin, Jennifer K. Lodge

University of Massachusetts Medical School Faculty Publications

Cryptococcus neoformans can cause fatal meningoencephalitis in patients with AIDS or other immune-compromising conditions. Current antifungals are suboptimal to treat this disease, therefore, novel targets and new therapies are needed. Previously, we have shown that chitosan is a critical component of the cryptococcal cell wall, is required for survival in the mammalian host, and that chitosan deficiency results in rapid clearance from the mammalian host. We had also identified several specific proteins that were required for chitosan biosynthesis, and we hypothesize that screening for compounds that inhibit chitosan biosynthesis would identify additional genes/proteins that influence chitosan biosynthesis.


Persistent Inflammation During Anti-Tuberculosis Treatment With Diabetes Comorbidity, Nathella Pavan Kumar, Kiyoshi F. Fukutani, Basavaradhya S. Shruthi, Thabata Alves, Paulo S. Silveira-Mattos, Michael S. Rocha, Kim West, Mohan Natarajan, Vijay Viswanathan, Subash Babu, Bruno B. Andrade, Hardy Kornfeld Jul 2019

Persistent Inflammation During Anti-Tuberculosis Treatment With Diabetes Comorbidity, Nathella Pavan Kumar, Kiyoshi F. Fukutani, Basavaradhya S. Shruthi, Thabata Alves, Paulo S. Silveira-Mattos, Michael S. Rocha, Kim West, Mohan Natarajan, Vijay Viswanathan, Subash Babu, Bruno B. Andrade, Hardy Kornfeld

Open Access Articles

Diabetes mellitus (DM) increases risk for pulmonary tuberculosis (TB) and adverse treatment outcomes. Systemic hyper-inflammation is characteristic in people with TB and concurrent DM (TBDM) at baseline, but the impact of TB treatment on this pattern has not been determined. We measured 17 plasma cytokines and growth factors in longitudinal cohorts of Indian and Brazilian pulmonary TB patients with or without DM. Principal component analysis revealed virtually complete separation of TBDM from TB individuals in both cohorts at baseline, with hyper-inflammation in TBDM that continued through treatment completion at six months. By one year after treatment completion, there was substantial ...