Discovery of cahuitamycins as biofilm inhibitors derived from a convergent biosynthetic pathway

Pathogenic microorganisms often have the ability to attach to a surface, building a complex matrix where they colonize to form a biofilm. This cellular superstructure can display increased resistance to antibiotics and cause serious, persistent health problems in humans. Here we describe a high-throughput in vitro screen to identify inhibitors of Acinetobacter baumannii biofilms using a library of natural product extracts derived from marine microbes. Analysis of extracts derived from Streptomyces gandocaensis results in the discovery of three peptidic metabolites (cahuitamycins A–C), with cahuitamycin C being the most effective inhibitor (IC50=14.5 μM). Biosynthesis of cahuitamycin C proceeds via a convergent biosynthetic pathway, with one of the steps apparently being catalysed by an unlinked gene encoding a 6-methylsalicylate synthase. Efforts to assess starter unit diversification through selective mutasynthesis lead to production of unnatural analogues cahuitamycins D and E of increased potency (IC50=8.4 and 10.5 μM).Great Lakes Regional Center of Excellence for Biodefense and Emerging Infectious Diseases/[U54 AI57153]/GLRCE/Estados UnidosArmy Research Office/[W911NF-12-1-0059]/ARO/Estados UnidosNational Institutes of Health/[1R01GM098350]/NIH/Estados UnidosInternational Cooperative Biodiversity Groups-Fogarty International Center/[U01 TW007404]/ICBG/Estados UnidosUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones en Productos Naturales (CIPRONA

Mycobacterium avium-intracellulare otomastoiditis in a young AIDS patient: case report and review of the literature [Corrigendum]

Viehman JA, Khalil D, Barhoma C, Hanna RM. HIV/AIDS—Research and Palliative Care. 2013;5:61–66.On page 61 in the abstract, "Otomastoiditis secondary to MAI is extremely rare in adults and has been reported in only four case reports and one case series previously" should have been "Otomastoiditis secondary to MAI is predominantly a pediatric disease and a rare entity in general. It has been reported in three case reports and one case series in pediatric patients, and now in this case report of an adult patient with HIV."On page 62, 4th paragraph of the introduction, "A literature review performed for MAI mastoiditis and otomastoiditis showed only four cases reported in the literature for adult patients, as well as a case series in four children" should have been "A literature review for MAI mastoiditis and otomastoiditis showed three pediatric case reports and one pediatric case series of four children."On page 64, 2nd paragraph of the discussion section, "MAI otomastoiditis in an immunosuppressed adult is thus a very noteworthy presentation, especially since until now it has been reported in only three adults with AIDS" should have been "MAI otomastoiditis in an immunocompromised adult is very unusual, since it has mostly been reported in pediatric patients previously."Read the original articl