Introducing the ArsR-Regulated Arsenic Stimulon

Abstract

The microbial ars operon encodes the primary bacterial defense response to the environmental toxicant, arsenic. An important component of this operon is the arsR gene, which encodes ArsR, a member of the family of proteins categorized as DNA-binding transcriptional repressors. As currently documented, ArsR regulates its own expression as well as other genes in the same ars operon. This study examined the roles of four ArsR proteins in the well-developed model Gram-negative bacterium Agrobacterium tumefaciens 5A. RNASeq was used to compare and characterize gene expression profiles in ± arsenite-treated cells of the wild-type strain and in four different arsR mutants. We report that ArsR-controlled transcription regulation is truly global, extending well beyond the current ars operon model, and includes both repression as well as apparent activation effects. Many cellular functions are significantly influenced, including arsenic resistance, phosphate acquisition/metabolism, sugar transport, chemotaxis, copper tolerance, iron homeostasis, and many others. While there is evidence of some regulatory overlap, each ArsR exhibits its own regulatory profile. Furthermore, evidence of a regulatory hierarchy was observed; i.e. ArsR1 represses arsR4, ArsR4 activates arsR2, and ArsR2 represses arsR3. Additionally and unexpectedly, aioB (arsenite oxidase small subunit) expression was shown to be under partial positive control by ArsR2 and ArsR4. Summarizing, this study demonstrates the regulatory portfolio of arsenite-activated ArsR proteins and includes essentially all major cellular functions. The broad bandwidth of arsenic effects on microbial metabolism assists in explaining and understanding the full impact of arsenic in natural ecosystems, including the mammalian gut.

Different Regulatory Strategies of Arsenite Oxidation by Two Isolated Thermus tengchongensis Strains From Hot Springs

“…Compared with strain 15Y, strain 15W lacks a complete ArsR family regulatory gene, due to this gene being truncated as determined by sequence alignment ( Figure 4 ). The ArsR family is a trans-acting repressor with other potential regulatory functions ( Kang et al, 2016 ; Rawle et al, 2021 ). The absence of regulatory function in strain 15W could explain why the two strains exhibited differences in As[III] oxidation ( Nei et al, 2010 ).…”

“…To our best knowledge, all isolated Thermus strains bearing aioBA genes except for 15W have regulatory genes upstream of the aio operon by analyzing existing genomes. Even though ArsR family members have been reported in the regulation of As oxidation in different taxa, they also contain a AioRS two-component system at the upstream of aioBA ( Moinier et al, 2014 ; Rawle et al, 2021 ). Besides AioRS, AioX, a periplasmic As[III]-binding protein, can also regulate As[III] oxidation ( Liu et al, 2012 ).…”

Transcriptional control ofhgcABby an ArsR-like regulator inPseudodesulfovibrio mercuriiND132

“…ArsR/SmtB family regulons may not always be associated with heavy metal resistance or arsenic transformations. In addition to regulating arsenic resistance, ArsR regulators have also been shown to influence many other cellular functions in the presence of As(III), including phosphate acquisition/metabolism, sugar transport, chemotaxis, copper tolerance, and iron homeostasis (68). Regulators in the ArsR/SmtB HTH family may also be responsive to substrates other than heavy metals and metalloids.…”

Navigating a Two-Way Street: Metal Toxicity and the Human Gut Microbiome

“…The known microbial influences on the human toxicity of iAs and MeHg may only be the tip of the iceberg. 84 , 85 In natural environments, for example, the As defense systems of soil and aquatic bacteria regulate an exceptionally wide range of cellular processes beyond iAs methylation, including sugar transport, copper tolerance, and iron homeostasis. 84 Walk says this fact—along with recent rodent findings 86 —suggests that microbes in the human gut may transform iAs in additional ways that indirectly influence toxicity, perhaps by producing arsenicals that more easily cross cell membranes.…”

“… 84 , 85 In natural environments, for example, the As defense systems of soil and aquatic bacteria regulate an exceptionally wide range of cellular processes beyond iAs methylation, including sugar transport, copper tolerance, and iron homeostasis. 84 Walk says this fact—along with recent rodent findings 86 —suggests that microbes in the human gut may transform iAs in additional ways that indirectly influence toxicity, perhaps by producing arsenicals that more easily cross cell membranes. “We think the total microbial influence on arsenic biochemistry is larger than the host’s and likely involves many different types of biotransformation,” adds Walk.…”