The widespread distribution among bacterial populations of antibiotic resistance has preserved or even increased the number of harmful bacteria involved in infections. Indeed, and despite previous reports, infectious diseases are now one of the most prominent health issues, partially due to the rising number of phenotypes of antibiotic resistance that cause bacterial infection.
Virulent bacteria have developed their phenotype in close association with their natural hosts, over a long evolutionary path. Most virulence determinants are either found in clusters of chromosomal genes (pathogenicity islands) or harbored in accessory genetic elements such as plasmids and phages. This indicates that evolution from an a virulent lifestyle to pathogenicity also includes the acquirement of foreign pieces of DNA . However, these pathogenicity factors should be introduced in an organism that is ecologically compatible with the potential host in order for the organism to be a true pathogen. In addition , in some cases it is not an acquisition but a deletion ("black holes" associated with virulence) that is required to become a pathogen.
Indeed, any change in lifestyle has a biological cost, as functions required in one habitat can create a burden in another habitat and could be counter-selected therefore. Acquisition of a virulence phenotype may then require the acquisition of some different islands of pathogenicity and the loss of some regions of chromosome DNA. Thus, the development of a pathogen by acquiring unique pathogenic elements in ecologically stable host-adapted bacterial genomes has likely taken place over a long evolutionary period.
During infection, some virulent bacteria base their pathogenic properties on an intracellular way of life. Internalization can be needed to induce inflammatory cytokines and cause damage to the tissue by either inducing necrotic or apoptotic responses. A striking example is the apoptosis of pathogens such as Shigella Mediated macrophages that both inhibit antibacterial effects and cause inflammation of these cells. Bacteria can migrate from cell to cell without direct interaction with the extracellular environment in some well-characterized cases, thereby avoiding the immune system and interacting with antibiotics that do not reach mammalian cells.
Several families of antibiotics are not that much permeable through Mammalian cells. Even if the antibiotic enters the mammalian cells, intracellular growth might induce a transient antibiotic-resistant phenotype, a situation that has been described for Legionella pneumophi. The position inside the host can unspecifiably alter the bacterial organism 's susceptibility to antibiotics. Haemophilus influenzae produced in animals undergoes modifications in proteins that bind penicillin, as the metabolism of peptidoglycan is directly influenced by the environment and Salmonella peptidoglycan Is significantly altered for intracellular bacteria. Although the impact of these changes on the susceptibility of antibiotics has not been thoroughly studied, it is likely that these changes in metabolism may alter the action of antibiotics such as beta lactams against bacteria that develop throughout infection. Intracellular localisation can then allow bacteria to maintain a pheno
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