RESUMO
Microorganisms reside in diverse environmental communities where interactions become indispensable due to close physical associations. These interactions are driven by chemical communication among different microbial kingdoms, particularly between fungi and bacteria. Knowledge about these communication signals provides useful information about the nature of microbial interactions and allows predictions of community development in diverse environments. Here, we provide an update on the role of small signalling molecules in fungal-bacterial interactions with focus on agricultural and medicinal environments. This review highlights the range of - and response to - diverse biochemicals produced by both kingdoms with view to harnessing their properties towards drug discovery applications.
Assuntos
Bactérias , Fungos , Agricultura , Bactérias/genética , Bactérias/metabolismo , Fungos/metabolismo , Interações MicrobianasRESUMO
Bacterial-fungal interactions are presumed to be mediated chiefly by small-molecule signals; however, little is known about the signaling networks that regulate antagonistic relationships between pathogens. Here, we show that the ralstonins, lipopeptides produced by the plant pathogenic bacteria Ralstonia solanacearum, interfere with germination of the plant-pathogenic fungus Aspergillus flavus by down-regulating expression of a cryptic biosynthetic gene cluster (BGC), named imq. Comparative metabolomic analysis of overexpression strains of the transcription factor ImqK revealed imq-dependent production of a family of tripeptide-derived alkaloids, the imizoquins. These alkaloids are produced via a nonribosomal peptide synthetase- (NRPS-)derived tripeptide and contain an unprecedented tricyclic imidazo[2,1-a]isoquinoline ring system. We show that the imizoquins serve a protective role against oxidative stress that is essential for normal A. flavus germination. Supplementation of purified imizoquins restored wildtype germination to a ΔimqK A. flavus strain and protected the fungus from ROS damage. Whereas the bacterial ralstonins retarded A. flavus germination and suppressed expression of the imq cluster, the fungal imizoquins in turn suppressed growth of R. solanacearum. We suggest such reciprocal small-molecule-mediated antagonism is a common feature in microbial encounters affecting pathogenicity and survival of the involved species.
Assuntos
Aspergillus flavus/fisiologia , Isoquinolinas/metabolismo , Lipopeptídeos/metabolismo , Peptídeo Sintases/metabolismo , Ralstonia solanacearum/patogenicidade , Aspergillus flavus/metabolismo , Aspergillus flavus/patogenicidade , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Isoquinolinas/farmacologia , Lipopeptídeos/farmacologia , Metabolômica , Família Multigênica , Doenças das Plantas/microbiologia , Ralstonia solanacearum/efeitos dos fármacos , Ralstonia solanacearum/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Esporos FúngicosRESUMO
IMPORTANCE: Nonsexual acute genital ulceration (NAGU) is a rare vulvar skin condition typically affecting girls and young women, characterized by acute onset of singular or multiple painful vaginal ulcers. The etiology of this ulcerative dermatosis has not been identified, although it has been associated with systemic infections. To our knowledge, this is the first report of an association with Lyme disease. OBSERVATIONS: A case of a woman with early disseminated Lyme disease presenting with NAGU is reported. A thorough workup ruled out other causes of genital ulceration, and the ulcers completely resolved after treatment with topical steroids and oral doxycycline. CONCLUSIONS AND RELEVANCE: Although the etiology of NAGU is unknown, the vulvar ulcers may result from an exuberant immune response to infection. Most patients with NAGU exhibit nonspecific symptoms such as myalgias and fever, suggesting an infectious agent, but the majority have no identifiable pathogen. In addition to previously reported associations with systemic infection, which are reviewed herein, Lyme disease should be considered in women presenting with acute-onset genital ulcers.