When our genome is targeted by pathogenic bacteria

Abstract

Eukaryotic cells repair thousands of lesions arising in the genome at each cell cycle. The most hazardous damage is likely DNA doublestrand breaks (DSB) that cleave the double helix backbone. DSBs occur naturally during T-cell receptor and immunoglobulin gene recombination in lymphocytes. DSBs can also arise as a consequence of exogenous stresses (e.g. ionizing irradiation, chemotherapeutic drugs, viruses) or oxidative processes. An increasing number of studies have reported that infection with pathogenic bacteria also alters the host genome, producing DSB and other modifications on DNA. This review focuses on recent data on bacteria-induced DNA damage and the known strategies used by these pathogens to maintain a physiological niche in the host. Even after DNA repair in infected cells, "scars" often remain on chromosomes and might generate genomic instability at the next cell division. Chronic inflammation in tissue, combined with infection and DNA damage, can give rise to genomic instability and eventually cancer. A functional link between the DNA damage response and the innate immune response has been recently established. Pathogenic bacteria also highjack the host cell cycle, often acting on the stability of the master regulator p53, or dampen the DNA damage response to support bacterial replication in an appropriate reservoir. Except in a few cases, the molecular mechanisms responsible for DNA lesions are poorly understood, although ROS release during infection is a serious candidate for generating DNA breaks. Thus, chronic or repetitive infections with genotoxic bacteria represent a common source of DNA lesions that compromise host genome integrity.

Chlorinated Water Modulates the Development of Colorectal Tumors with Chromosomal Instability and Gut Microbiota in Apc-Deficient Mice

“…Many studies have reported that infection with pathogenic bacteria can alter the host genome, producing double-strand breaks (DSBs) and other DNA modifications; even after DNA repair, chromosomes can remain scarred and cause genomic instability during the next round of cell division. Escherichia coli genotoxin induces DNA DSBs [ 36 ], while Pseudomonas aeruginosa induces single-strand breaks, DSBs, and oxidative DNA damage that activate a variety of DNA repair pathways [ 37 ]. The functional connection between the innate immunity and the DNA damage response has been demonstrated by many studies: for instance, Enterococcus faecalis —a Gram-positive intestinal commensal bacterium that produces extracellular superoxide—can polarize macrophages to induce a bystander effect that results in DSBs, tetraploidy, and CIN in target cells and can cause inflammation and colorectal carcinoma in interleukin (IL)-10 knockout mice [ 38 , 39 ].…”

Intracellular Growth and Morphological Characteristics of <i>Legionella pneumophila</i> during Invasion and Proliferation in Different Cells

“…The downregulation or inhibition of p53 could help Neisseria gonorrhoeae, Listeria monocytogenes, Shigella flexneri to survive and multiply in the host cytoplasm. 32) Nevertheless, the results from our study (including proliferation curve and morphologic study) indicated that mutated p53 of MDA-MB231 had no obvious effect on intracellular growth of L. pneumophila.…”

Bacterial DNA damage effectors in host cells

“…Завершая обзор, следует отметить, что приведенные сведения о генотоксических эффектах отдельных представителей микробиоты изложены нами в краткой форме, без детального описания известных или предполагаемых молекулярных механизмов действия бактериальных эффекторов на ДНК клеток организмахозяина. Более подробную информацию можно получить, ознакомившись с соответствующими обзорами, опубликованными за последнее время [11,65,[88][89][90]. Здесь мы хотим подчеркнуть, что с учетом длительной коэволюции микробиоты с высшими организмами влияние бактериальной инфекции на целостность генома хозяина не является неожиданным.…”