AUTHOR=Saldaña-Ahuactzi Zeus , Soria-Bustos Jorge , Martínez-Santos Verónica I. , Yañez-Santos Jorge A. , Martínez-Laguna Ygnacio , Cedillo-Ramirez María Lilia , Puente José L. , Girón Jorge A. 

TITLE=The Fis Nucleoid Protein Negatively Regulates the Phase Variation fimS Switch of the Type 1 Pilus Operon in Enteropathogenic Escherichia coli

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.882563

DOI=10.3389/fmicb.2022.882563

ISSN=1664-302X

ABSTRACT=<p>In <italic>Escherichia coli</italic> the expression of type 1 pili (T1P) is determined by the site-specific inversion of the <italic>fimS</italic> ON–OFF switch located immediately upstream of major fimbrial subunit gene <italic>fimA</italic>. Here we investigated the role of virulence (Ler, GrlR, and GrlA) and global regulators (H-NS, IHF, and Fis) in the regulation of the <italic>fimS</italic> switch in the human enteropathogenic <italic>E. coli</italic> (EPEC) O127:H6 strain E2348/69. This strain does not produce detectable T1P and PCR analysis of the <italic>fimS</italic> switch confirmed that it is locked in the OFF orientation. Among the regulator mutants analyzed, only the ∆<italic>fis</italic> mutant produced significantly high levels of T1P on its surface and yielded high titers of agglutination of guinea pig erythrocytes. Expression analysis of the <italic>fimA</italic>, <italic>fimB</italic>, and <italic>fimE</italic> promoters using <italic>lacZ</italic> transcriptional fusions indicated that only P<italic>fimA</italic> activity is enhanced in the absence of Fis. Collectively, these data demonstrate that Fis is a negative regulator of T1P expression in EPEC and suggest that it is required for the FimE-dependent inversion of the <italic>fimS</italic> switch from the ON-to-OFF direction. It is possible that a similar mechanism of T1P regulation exists in other intestinal and extra-intestinal pathogenic classes of <italic>E. coli</italic>.</p>