Could β-Lactam Antibiotics Block Humoral Immunity?

Abstract

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. β-lactamases can cleave β-lactam antibiotics by blocking their activity. 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. 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. 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. Thus in humans, SNM1C/Artemis mutation is associated with severe combined immunodeficiency characterized by hypogammaglobulinemia deficient cellular immunity and opportunistic infections. 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. By analogy, the question arises as to whether β-lactam antibiotics can block the SNM1C/Artemis protein in humans inducing transient immunodeficiency. We reviewed here the literature data supporting this hypothesis based on in silico, in vitro and in vivo evidences. 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.

Assessment of the targeted effect of Sijunzi decoction on the colorectal cancer microenvironment via the ESTIMATE algorithm

“…The results of C5 enrichment analysis in the high immune score group suggested that the infiltration of immune cells in the TME of CRC might be related to the following biological functions: amide binding, response to wounding, endosomal part, calcium ion transmembrane transport, and endocytic vesicle (Fig 2D). The biological function of amide binding was of the highest NES in the high immune score (Fig 2C, S1 Appendix), which indicated that this gene set might regulate the immune response in patients with CRC by inducing related amide binding, that was consistent with the previous research [43].…”

Antibiotic Therapy, Antibiotic Resistance, Drug-Induced Pathomorphosis, and Evolutionary Medicine

“…In vitro studies showed that some β-lactam antibiotics, namely third-generation cephalosporins and ampicillin, inhibit metallo-β-lactamase proteins SNM1 (sensitive to nitrogen mustard) A & B and SNM1C/Artemis protein complex. The authors of the publication [71] claim that β-lactam antibiotics (cephalosporins, ampicillin) can block the SNM1C/Artemis protein in humans, causing transient immunodeficiency.…”

Effect of gluten-free diet and antibiotics on murine gut microbiota and immune response to tetanus vaccination

“…Th1, Th2, and T reg [ 11 ], and it is known in mice that antibiotic-driven dysregulation of the GM can modulate immune responses to vaccines in early [ 33 ] and in late life [ 34 ]. Ampicillin has been hypothesized to block humoral vaccine responses in humans, because its blocking of a specific protein the lack of may induce a transient immunodeficiency [ 35 ]. Also, bacterial flagellin stimulation of Toll-like receptor 5 (TLR5) is needed to drive antibody production after influenza vaccination [ 36 ].…”