![]() Lipid/Phospholipid degradation, metabolism Severe combined immunodeficiency autosomal recessive T-cell-negative/B cell-negative/NKcell-positive with sensitivity to ionizing radiation (RSSCID), Severe combined immunodeficiency Athabaskan type (SCIDA),Omenn syndrome (OS) Mutations: impaired nuclear focus formation, reduced interaction with PIAS and increased sensitivity to cisplatinĪdaptive immunity DNA damage, recombination, repair/DNA crosslink repair Hydrogen sulfide metabolic processĬell cycle, DNA damage/DNA crosslink repair This is the case for the SNM1C/Artemis mutation that induces severe combined immunodeficiency characterized by hypersensitivity to ϒ rays irradiation and severe opportunistic infections (see next chapter) ( 28). While the physiological enzymatic role of most of them remains unknown, mutation of some hMBLs has been identified as linked to clinical disease ( Table 1) ( 28– 31). In human, 18 metallo-β-lactamases (hMBLs) enzymes have been identified ( Table 1) ( 28). Two mechanistically distincts superfamilies of β-lactamases with two distincts ancestors are described, the nucleophilic serine β-lactamases (class A/C/D) and the zinc ion dependent metallo-β-lactamases (class B) ( 17, 25– 27). β-lactamases enzymes hydrolyse the β-lactam antibiotics and may also have different nuclease and hydrolases activities ( 17– 24). First of all, it works by inhibiting the bacterial peptidoglycan cell wall synthesis ( 16). Β-lactam antibiotics may have multiple activities. Nevertheless the direct effect of β-lactam antibiotics on immune cells remains poorly understood ( 9– 15). In addition, its utilization prior to anticancer immunotherapy was associated with a worse clinical response ( 6– 8). However, parenteral use of β-lactam antibiotics was associated, in human, with an increased risk of complications such as candidemia, especially in the presence of catheters ( 5). In clinical practice, β-lactam antibiotics are increasingly used to treat pulmonary, urinary, skin, osteo-articular and cardio-vascular infections ( 2, 4). Β-lactam antibiotics remain the cornerstone of the antibacterial arsenal, being the most prescribed and the most important class of antibiotics in terms of sales ( 1– 3). Understanding the impact of β-lactam antibiotics on the immune cell will offer new therapeutic clues and new clinical approaches in oncology, immunology, and infectious diseases. We reviewed here the literature data supporting this hypothesis based on in silico, in vitro and in vivo evidences. By analogy, the question arises as to whether β-lactam antibiotics can block the SNM1C/Artemis protein in humans inducing transient immunodeficiency. ![]() While catalytic site of hMBLs and especially that of the SNM1 family is highly conserved, in vitro studies showed that some β-lactam antibiotics, and precisely third generation of cephalosporin and ampicillin, inhibit the metallo-β-lactamase proteins SNM1A & B and the SNM1C/Artemis protein complex. Thus in humans, SNM1C/Artemis mutation is associated with severe combined immunodeficiency characterized by hypogammaglobulinemia deficient cellular immunity and opportunistic infections. ![]() ![]() The SNM1C/Artemis protein is precisely associated in the V(D)J segments rearrangement, that leads to immunoglobulin (Ig) and T-cell receptor variable regions, which have a crucial role in the immune response. While the physiological role of most of them remains unknown, it is well established that the SNM1A, B and C proteins are involved in DNA repair. Two distincts superfamilies of β-lactamases are described, the serine β-lactamases and the zinc ion dependent metallo-β-lactamases. In human, 18 metallo-β-lactamases encoding genes (hMBLs) have been identified. ![]() β-lactamases can cleave β-lactam antibiotics by blocking their activity. It has been reported that treatment with β-lactam antibiotics induces leukopenia and candidemia, worsens the clinical response to anticancer immunotherapy and decreases immune response to vaccination. ![]()
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