RNA modification enzymes encoded by the gid operon: Implications in biology and virulence of bacteria

Shippy, Daniel C.; Fadl, Amin A.

doi:10.1016/j.micpath.2015.09.008

Cited by 20 publications

(18 citation statements)

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“…The results are also consistent with a study demonstrating that lowering ribosomal synthesis increases resistance to ciprofloxacin by restoring an optimal balance between protein and DNA synthesis levels during DNA stress (39)). Most notable among the insertions identified were those in gidA , which is part of a complex involved in 5-methylaminomethyl-2-thiouridine (mnm 5 s 2 U34) modification of tRNAs (Data Set S1; (40)). We have previously identified this gene as an additional target of mutations bypassing drug hypersensitivity resulting from loss of bfmRS (34), indicating the tight connection between mutations in this gene and drug resistance.…”

Section: Resultsmentioning

confidence: 99%

The landscape of intrinsic and evolved fluoroquinolone resistance inAcinetobacter baumanniiincludes suppression of drug-induced prophage replication

Geisinger

Vargas-Cuebas

Mortman

et al. 2018

Preprint

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Section: Resultsmentioning

confidence: 99%

The landscape of intrinsic and evolved fluoroquinolone resistance inAcinetobacter baumanniiincludes suppression of drug-induced prophage replication

Geisinger

Vargas-Cuebas

Mortman

et al. 2018

Preprint

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“…In our study, a transposon insertion in the gibB gene also resulted in a pellicle‐negative phenotype. The role of the gibAB operon in virulence and stress response has been recently reviewed (Shippy & Fadl, ), and deletion mutants of these genes have been shown to have a deleterious effect on biofilm formation in Pseudomonas fluorescens (Zhang et al., ), and Streptococcus mutans (Li et al., ). We contribute the observation that this operon is also important for biofilm formation in B. cereus .…”

Section: Resultsmentioning

confidence: 99%

A transposon mutant library of Bacillus cereus ATCC 10987 reveals novel genes required for biofilm formation and implicates motility as an important factor for pellicle‐biofilm formation

et al. 2017

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Bacillus cereus is one of the most common opportunistic pathogens causing foodborne illness, as well as a common source of contamination in the dairy industry. B. cereus can form robust biofilms on food processing surfaces, resulting in food contamination due to shedding of cells and spores. Despite the medical and industrial relevance of this species, the genetic basis of biofilm formation in B. cereus is not well studied. In order to identify genes required for biofilm formation in this bacterium, we created a library of 5000 + transposon mutants of the biofilm‐forming strain B. cereus ATCC 10987, using an unbiased mariner transposon approach. The mutant library was screened for the ability to form a pellicle biofilm at the air‐media interface, as well as a submerged biofilm at the solid‐media interface. A total of 91 genes were identified as essential for biofilm formation. These genes encode functions such as chemotaxis, amino acid metabolism and cellular repair mechanisms, and include numerous genes not previously known to be required for biofilm formation. Although the majority of disrupted genes are not directly responsible for motility, further investigations revealed that the vast majority of the biofilm‐deficient mutants were also motility impaired. This observation implicates motility as a pivotal factor in the formation of a biofilm by B. cereus. These results expand our knowledge of the fundamental molecular mechanisms of biofilm formation by B. cereus.

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“…Mutations in the tRNA modification enzyme MnmG/GidA also influence bacterial virulence, presumably because they increase the frequency of a two-base frameshift during translation of mRNA ( Shippy and Fadl, 2015 ; Gao et al, 2016 ). This led to suggestions that a gidA deletion could be used as an attenuated vaccine candidate ( Shippy and Fadl, 2012 ).…”

Section: Mutations In Folate- and Flavin-dependent Methyltransferasesmentioning

confidence: 99%

Unique Features and Anti-microbial Targeting of Folate- and Flavin-Dependent Methyltransferases Required for Accurate Maintenance of Genetic Information

et al. 2018

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Comparative genome analyses have led to the discovery and characterization of novel flavin- and folate-dependent methyltransferases that mainly function in DNA precursor synthesis and post-transcriptional RNA modification by forming (ribo) thymidylate and its derivatives. Here we discuss the recent literature on the novel mechanistic features of these enzymes sometimes referred to as “uracil methyltransferases,” albeit we prefer to refer to them as (ribo) thymidylate synthases. These enzyme families attest to the convergent evolution of nucleic acid methylation. Special focus is given to describing the unique characteristics of these flavin- and folate-dependent enzymes that have emerged as new models for studying the non-canonical roles of reduced flavin co-factors (FADH2) in relaying carbon atoms between enzyme substrates. This ancient enzymatic methylation mechanism with a very wide phylogenetic distribution may be more commonly used for biological methylation reactions than previously anticipated. This notion is exemplified by the recent discovery of additional substrates for these enzymes. Moreover, similar reaction mechanisms can be reversed by demethylases, which remove methyl groups e.g., from human histones. Future work is now required to address whether the use of different methyl donors facilitates the regulation of distinct methylation reactions in the cell. It will also be of great interest to address whether the low activity flavin-dependent thymidylate synthases ThyX represent ancestral enzymes that were eventually replaced by the more active thymidylate synthases of the ThyA family to facilitate the maintenance of larger genomes in fast-growing microbes. Moreover, we discuss the recent efforts from several laboratories to identify selective anti-microbial compounds that target flavin-dependent thymidylate synthase ThyX. Altogether we underline how the discovery of the alternative flavoproteins required for methylation of DNA and/or RNA nucleotides, in addition to providing novel targets for antibiotics, has provided new insight into microbial physiology and virulence.

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RNA modification enzymes encoded by the gid operon: Implications in biology and virulence of bacteria

Cited by 20 publications

References 123 publications

The landscape of intrinsic and evolved fluoroquinolone resistance inAcinetobacter baumanniiincludes suppression of drug-induced prophage replication

The landscape of intrinsic and evolved fluoroquinolone resistance inAcinetobacter baumanniiincludes suppression of drug-induced prophage replication

A transposon mutant library of Bacillus cereus ATCC 10987 reveals novel genes required for biofilm formation and implicates motility as an important factor for pellicle‐biofilm formation

Unique Features and Anti-microbial Targeting of Folate- and Flavin-Dependent Methyltransferases Required for Accurate Maintenance of Genetic Information

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