anthracis colonies; VC: carried out statistical analysis; LM: collaborated to the experimental studies conducted in ABL3 facilities; DB: collaborated to the experimental studies conducted in ABL3 facilities; CP: prepared all media for culturing and isolation of B. anthracis; RA: revised the experimental Selleckchem Opaganib design and collaborated on the report of the manuscript; MHJ: revised the experimental design and collaborated on the report of the manuscript. All authors

read and approved the final manuscript.”
“Background Many secondary metabolites play important ecological roles in the interactions between microbes and other organisms. Some, such as the host-selective toxins, are virulence factors for plant pathogenic fungi [1]. Two genera, Cochliobolus and Alternaria, both in the Pleosporaceae of the Dothideomycetes, have particularly exploited this strategy to increase their pathogenic fitness and to extend their host range to new species and strains of crop plants ranging from cereals (maize, oats) to dicotyledonous plants (strawberry, citrus, tobacco, tomato) [2–4]. HC-toxin is a cyclic tetrapeptide of structure cyclo(D-Pro-L-Ala-D-Ala-L-Aeo), where Aeo stands for 2-amino-9,10-epoxi-8-oxo-decanoic acid. HC-toxin is a host-selective toxin LY2109761 mouse that endows the pathogenic fungus Cochliobolus carbonum with exceptional virulence on maize varieties that

lack a functional copy of HM1 and/or HM2, both of which encode a carbonyl reductase that detoxifies HC-toxin [5]. A minority of natural isolates of C. carbonum, designated race 1, make HC-toxin [6]. Only maize lines of genotype hm1/hm1, hm2/hm2 are sensitive to HC-toxin and hence susceptible to race 1 isolates of C. carbonum. Because all grasses have functional orthologs of HM1, HC-toxin-producing pathogens (not necessarily C. carbonum) have apparently exerted significant selective pressure on plants in the Poaceae throughout their evolutionary history [7]. The central enzyme in HC-toxin biosynthesis,

HTS1, is a four-module nonribosomal peptide synthetase (NRPS) containing one epimerase domain [5]. Other known genes involved in HC-toxin biosynthesis include TOXA, encoding a member of the major facilitator superfamily of transporters; TOXC, encoding a fatty acid synthase beta subunit; TOXE, encoding a pathway-specific Liothyronine Sodium transcription factor; TOXF, encoding a putative branched chain amino acid aminotransferase; and TOXG, encoding an alanine racemase. A seventh gene found in the TOX2 locus, TOXD, encodes a predicted short-chain alcohol dehydrogenase, but its disruption gave no phenotype in HC-toxin production or virulence [5]. The genes involved in HC-toxin biosynthesis, called collectively TOX2, are organized into a diffuse cluster that spans >500 kb. All of the known genes are duplicated or triplicated within this region, with some variation in copy number and chromosomal location among different race 1 strains [8, 9] .