The methylation-independent mismatch repair machinery in Pseudomonas aeruginosa

Abstract

Over the last 70 years, we’ve all gotten used to an Escherichia coli -centric view of the microbial world. However, genomics, as well as the development of improved tools for genetic manipulation in other species, is showing us that other bugs do things differently, and that we cannot simply extrapolate from E. coli to everything else. A particularly good example of this is encountered when considering the mechanism(s) involved in DNA mismatch repair by the opportunistic human pathogen, Pseudomonas aeruginosa (PA). This is a particularly relevant phenotype to examine in PA, since defects in the mismatch repair (MMR) machinery often give rise to the property of hypermutability. This, in turn, is linked with the vertical acquisition of important pathoadaptive traits in the organism, such as antimicrobial resistance. But it turns out that PA lacks some key genes associated with MMR in E. coli , and a closer inspection of what is known (or can be inferred) about the MMR enzymology reveals profound differences compared with other, well-characterized organisms. Here, we review these differences and comment on their biological implications.

Restriction Endonuclease-based Modification-Dependent Enrichment (REMoDE) of DNA for Metagenomic Sequencing

“…We soon learned that OP50 is derived from B strain E. coli (45). Also to be noted is that while Dam methyltransferases are indeed widespread (though not ubiquitous (46)) within Gammaproteobacteria , Dcm methyltransferases are confined to genera closely related to Escherichia which may serve as an advantage or disadvantage depending on the organismal DNA to be enriched for (40). Since the Dam motif is shorter than the Dcm motif, it is found more frequently in any given genome.…”

The role of the Pseudomonas aeruginosa hypermutator phenotype on the shift from acute to chronic virulence during respiratory infection

“…The discrepancy between clinical and experimental observations suggests that the hypermutator phenotype may be critical for bacterial adaption or survival during CRI. High mutation rates have been shown to be beneficial in early colonization and mutator alleles can become fixed in a fraction of the population due to their evolutionary advantage, even though randomly occurring deleterious mutations at secondary sites can TABLE 1 Pa MMR genes and their respective functions, along with common point mutation positions resulting in protein inactivation (Oliver et al, 2002a;Hogardt et al, 2006;On and Welch, 2021).…”

Microbial Musings – December 2021

“…This was a fascinating review and I found myself contrasting its revelations with what I know about how bacteria solve similar problems in the uptake, efflux and storage of metals such as iron, zinc and copper, which of course in these organisms is even more complex as they also have to be moved between different organelles. The second, from Yue Yuan On and Microbiology Senior Editor Martin Welch, comprises an analysis of DNA mismatch repair (MMR) machinery in the human pathogen P. aeruginosa , which they argue differs significantly from that of its relative E. coli and is very important for the evolution of this pathogen in vivo – a subject that demands further study [ 21 ].…”