MarR Family Transcription Factors from Burkholderia Species: Hidden Clues to Control of Virulence-Associated Genes

Abstract

SUMMARY Species within the genus Burkholderia exhibit remarkable phenotypic diversity. Genomic plasticity, including genome reduction and horizontal gene transfer, has been correlated with virulence traits in several species. However, the conservation of virulence genes in species otherwise considered to have limited potential for infection suggests that phenotypic diversity may not be explained solely on the basis of genetic diversity. Instead, differential organization and control of gene regulatory networks may underlie many phenotypic differences. In this review, we evaluate how regulation of gene expression by members of the multiple antibiotic resistance regulator (MarR) family of transcription factors may contribute to shaping the physiological diversity of Burkholderia species, with a focus on the clinically relevant human pathogens. All Burkholderia species encode a relatively large number of MarR proteins, a feature common to bacteria that must respond to environmental changes such as those associated with host invasion. However, evolution of gene regulatory networks has likely resulted in orthologous transcription factors controlling disparate sets of genes. Adaptation to, and survival in, diverse habitats, including a human or plant host, is key to the success of Burkholderia species as (opportunistic) pathogens, and recent reports suggest that control of virulence-associated genes by MarR proteins features prominently among the survival strategies employed by these species. We suggest that identification of MarR regulons will contribute significantly to clarification of virulence determinants and phenotypic diversity.

The role of rpoS in the regulation of Vibrio alginolyticus virulence and the response to diverse stresses

“…As we know, environmental adaptation plays an important role in pathogens to survive in natural environment or invade hosts (Høyland-Kroghsbo, Muñoz, & Bassler, 2018;Rossi, Paroni, & Landini, 2018). As a result, in order to better understand the virulence mechanism of pathogens, many studies were devoted to elucidating key genes related to stress resistance (Gupta et al, 2019;Tian et al, 2008). Among these, RpoS was proved to enable transcription of genes associated with the general stress response and stationary phase metabolism (Campos-Gomez & Benitez, 2018;Park, Nam, Kweon, & Shin, 2018).…”

MarR family proteins are important regulators of clinically relevant antibiotic resistance

“…While some structural and genetic studies have led to the identification and initial characterization of a few clinically important MarR family regulators including MarR and MprA from E. coli , MexR from P. aeruginosa , FarR from N. gonorrhoeae , and MepR from S. aureus , much remains to be elucidated. Specifically, molecular mechanisms of drug binding and induction of many MarR proteins from multiple pathogens, including those of other important pathogens such as Burkholderia species, have yet to be characterized fully. Further structural and biochemical studies are needed to determine the molecular basis for MarR regulator‐mediated antimicrobial resistance in myriad pathogens that ultimately could lead to the development of novel classes of compounds that in lieu of targeting a critical cellular process or an efflux pump, locks strategic members of the MarR family into their high affinity, DNA‐binding forms thereby inhibiting expression of key efflux pumps and allowing the accumulation of killing concentrations of one or more classes of antimicrobials.…”

Caracterização cinética do fator de transcrição do sistema Ohr/OhrR de Pseudomonas aeruginosa e análise de respostas fenotí­picas e imunológicas

“…A interação patógeno-hospedeiro nem sempre resulta em doença. O resultado depende da interação inicial, que pode ser: comensalismo, colonização, persistência e, finalmente, infecção, resultando em prejuízos para o hospedeiro 12 .…”

“…Diferentes autores sugerem que OhrR pertença a um regulon que controle a expressão de outros genes 12,62 , além de seu próprio gene ohrR por autorregulação e a de ohr. De fato, o grupo liderado pelo Dr. José Freire da Silva Neto, em colaboração com nosso grupo, mostrou recentemente que OhrR também regula a expressão de diguanilato ciclases, atuando em sinalização mediada por di-cGMP 63 .…”

“…De fato, o grupo liderado pelo Dr. José Freire da Silva Neto, em colaboração com nosso grupo, mostrou recentemente que OhrR também regula a expressão de diguanilato ciclases, atuando em sinalização mediada por di-cGMP 63 . Por outro lado, o gene ohrR pode ser regulado de maneira hierárquica, por OspR em P. aeruginosa 64 Além de OhrR, segundo Gupta (2018) 12 Esse patógeno foi descrito pela primeira vez em 1927, na Malásia 77 e uma de suas características é a produção de um antibiótico natural, violaceína, que pode ser útil no tratamento de alguns tipos de cânceres 71 e apresenta coloração violeta intenso, caracterizando as colônias 72 .…”