AUTHOR=Zhang Peipei , Wu Lili , Zhu Yanping , Liu Meng , Wang Yemin , Cao Guangxiang , Chen Xiu-Lan , Tao Meifeng , Pang Xiuhua 

TITLE=Deletion of MtrA Inhibits Cellular Development of Streptomyces coelicolor and Alters Expression of Developmental Regulatory Genes

JOURNAL=Frontiers in Microbiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.02013

DOI=10.3389/fmicb.2017.02013

ISSN=1664-302X

ABSTRACT=<p>The developmental life cycle of <italic>Streptomyces</italic> species includes aerial hyphae formation and spore maturation, two distinct developmental processes that are controlled, respectively, by two families of developmental regulatory genes, <italic>bld</italic> and <italic>whi</italic>. In this study, we show that the response regulator MtrA (SCO3013) is critical for normal development of aerial hyphae in <italic>S. coelicolor</italic> and related species. Δ<italic>mtrA,</italic> a deletion mutant of the response regulator gene <italic>mtrA</italic>, exhibited the bald phenotype typical of <italic>bld</italic> mutants defective in aerial mycelium formation, with formation either much delayed or absent depending on the culture medium. Transcriptional analysis indicated that MtrA activates multiple genes involved in formation of aerial mycelium, including <italic>chp</italic>, <italic>rdl</italic>, and <italic>ram</italic> genes, as well as developmental regulatory genes of the <italic>bld</italic> and <italic>whi</italic> families. However, the major regulatory gene <italic>bldD</italic> showed enhanced expression in Δ<italic>mtrA</italic>, suggesting it is repressed by MtrA. electrophoretic mobility shift assays indicated that MtrA binds upstream of several genes with altered expression in Δ<italic>mtrA</italic>, including <italic>bldD</italic> and <italic>whiI</italic>, and sequences similar to the consensus binding sequence for MtrA of another actinomycete, <italic>Mycobacterium tuberculosis</italic>, were found in the bound sites. A loosely conserved recognition sequence containing two short, direct repeats was identified for MtrA of <italic>S. coelicolor</italic> and was validated using mutational analysis. MtrA homologs are widely distributed among <italic>Streptomyces</italic> species, and as with <italic>S. coelicolor,</italic> deletion of the <italic>mtrA</italic> homologs <italic>sve_2757</italic> from <italic>S. venezuelae</italic> and <italic>sli_3357</italic> from <italic>S. lividans</italic> resulted in conditional bald morphology. Our study suggests a critical and conserved role for MtrA in <italic>Streptomyces</italic> development.</p>