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Host Defense and Parasite Evasion
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
One noteworthy defense strategy is the restriction-modification system in bacteria. A typical system couples an endonuclease with a modification enzyme. The endonuclease recognizes specific sequences in phage DNA and cleaves (or restricts) the DNA at these sites, thus disabling the phage. The modification enzyme, often a methyltransferase, adds a methyl group to the host bacterium’s DNA, thereby protecting it from endonuclease attack. This is a system of self–non-self recognition that can selectively disable non-self entities such as viruses. In response, phages have been selected to avoid using nucleotide sequences targeted by restriction enzymes. They may also incorporate unusual or modified nucleotides at target sites, or they may protect the sites by cloaking them in proteins. Alternatively, they may hijack host methyltransferases to methylate and thus protect their target sequences. Clearly, the classic elements of an arms race exist within this system.
Host Defense and Parasite Evasion
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2015
Eric S. Loker, Bruce V. Hofkin
One noteworthy defense strategy is the restriction modification system in bacteria. A typical system couples an endonuclease with a modification enzyme. The endonuclease recognizes specific sequences in phage DNA and cleaves the DNA at these sites, thus disabling the phage. The modification enzyme, often a methyltransferase, adds methyl group to the host bacterium’s DNA, thereby protecting it from endonuclease attack. This is a system of self-nonself recognition that can selectively disable nonself entities such as viruses. In response, phages have been selected to avoid using nucleotide sequences targeted by restriction enzymes. They may also incorporate unusual or modified nucleotides at target sites, or they may protect the sites by cloaking them in proteins. Alternatively, they may hijack host methytrans-ferases to methylate and thus protect their own target sequences. Clearly, the classic elements of an arms race exist within this system.
Bioengineering and the Idea of Precision Medicine
Published in Emmanuel A. Kornyo, A Guide to Bioethics, 2017
Restriction enzymes are naturally found in bacteria where they function as defensive apparatus against viral infections or foreign DNA by cutting them.6 Restriction enzymes are also known nucleases because they split or cleave DNA either at recognition sites or specific sites of the host bacteria. Because of their ability to “break,” “cut,” or “open” nucleic acids, they are often referred to as molecular scissors and have been significant in recombinant biotechnology. The cut may be a spontaneous single-stranded break (SSB) in a DNA sequence or protein, which could increase genetic instability and sometimes cause neurodegenerative diseases such as Spinocerebellar Ataxia. A SSB may also occur due to intracellular metabolites such as reactive oxygen. While these SSB occur frequently, the breaks are easily repaired by the DNA repair pathways. The cut may also be a double-stranded break (DSB) in the DNA sequence or protein which unlike SSB is rare. It is worth noting that DNAs have a natural or endogenous modification mechanism known as restriction modification system (RMS) that “repairs” damages or the molecular lesions internally. Once the repair mechanism is activated, it can result in either a homologous or nonhomologous recombination depending on the type of break in the DNA sequence. But the repair can also be done by bioengineering specific nucleases to repair the scar or the cleavage sites. In homologous repair, similar nucleotides or DNA molecules are exchanged or recombined in a double-strand break. This corrects aberrations or potentially harmful damages done to some genes during the process of cell division (meiosis). The nonhomologous mechanism also repairs DSB but does not use similar template during the repair process and the coded gene becomes nonfunctional among others. The process of gene editing involves the construction of nucleases that introduces DNA DSB at specific sites within a genome or gene of interest. This break or cut allows for gene editing technologies to be introduced: to turn off specific genes resulting in their loss of function in cells for therapeutic purposes or in some situations new copies of genes may be added for specific reasons such as bolstering the functions of a cluster of genes or individual genes.7
Exploration of the interplay between spatially distinct microbial habitats through comparative analysis
Published in Journal of Oral Microbiology, 2023
Hyunji Kim, Jin-Sil Hong, Pil-Young Yun, Kyung-Gyun Hwang, Keun-Suh Kim, Hyo-Jung Lee, Kyoung Un Park
In addition to the similarities in microbial composition and diversity across different habitat specimens, the results of functional pathway analyses using 16S rRNA metagenomics data revealed differences according to the progression of periodontitis. Saliva specimens, in particular, displayed differences in restriction enzyme functional pathways based on disease status. Restriction modification systems in bacteria play a crucial role not only in defense but also in maintaining population heterogeneity and facilitating adaptation to changing environmental conditions. They are also essential for the colonization of host tissues by pathogenic bacteria [49]. The 16S rRNA analysis, which was confined to the V3 and V4 regions, failed to identify restriction enzyme aberrations, which is significant in light of the pivotal role of such enzymes in bacterial evolution and ecology.
Genomic diversity of Helicobacter pylori populations from different regions of the human stomach
Published in Gut Microbes, 2022
Daniel James Wilkinson, Benjamin Dickins, Karen Robinson, Jody Anne Winter
In addition, restriction-modification system genes were identified as highly allelic. Furuta et al (2015),51 observed similar genetic diversity among restriction-modification associated genes using a comparative genetics approach with single colony isolates obtained from five families. Other studies have also observed restriction-modification system diversity between strains taken from different patients.11,52,53 Bacterial restriction-modification systems confer protection against invading foreign DNA54 but do not pose a barrier to homologous recombination.55 Restriction-modification systems can also influence gene expression56,57 and may have roles in adhesion and virulence.58,59 Diversity in restriction-modification genes could therefore play a role in niche adaptation and persistence.
Biological challenges of phage therapy and proposed solutions: a literature review
Published in Expert Review of Anti-infective Therapy, 2019
Katherine M Caflisch, Gina A Suh, Robin Patel
The most ubiquitous mechanism of defense among bacteria and archaea, RM systems detect and cleave foreign DNA, including phage double-stranded DNA, based on nucleotide methylation of host DNA [109]. (RM systems are considered not to degrade single-stranded DNA or RNA phage.) Harbored by more than 90% of prokaryotes according to some estimates, RM systems play a role in prokaryotic homeostasis analogous to the innate immune system of higher-order organisms [109]. Restriction-modification systems are comprised of two functional subunits – a restriction endonuclease which cleaves (degrades) un-methylated DNA, and a related methyltransferase which methylates host DNA [109]. Such epigenetic modification forms the basis for recognizing and sequestering foreign genomic material [109,110] and is phylogenetically conserved, with several hypotheses attempting to explain why this might be the case [109]. Korona et al. predicts that RM systems stave off global infection of the bacterial community upon phage introduction to allow for the expansion of genetically diverse bacterial sub-populations [111].