Integrated Metabolomic, Molecular Networking, and Genome Mining Analyses Uncover Novel Angucyclines From sp. RO-S4 Strain Isolated From Bejaia Bay, Algeria.

Multi-omic approaches have recently made big strides toward the effective exploration of microorganisms, accelerating the discovery of new bioactive compounds. We combined metabolomic, molecular networking, and genomic-based approaches to investigate the metabolic potential of the sp. RO-S4 strain isolated from the polluted waters of Bejaia Bay in Algeria.

Inhibition of the β-Lactamase Bla by Avibactam Improves the and Efficacy of Imipenem against Mycobacterium abscessus.

pulmonary infections are treated with a macrolide (clarithromycin or azithromycin), an aminoglycoside (amikacin), and a β-lactam (cefoxitin or imipenem). The triple combination is used without any β-lactamase inhibitor, even though produces the broad-spectrum β-lactamase Bla We determine whether inhibition of Bla by avibactam improves the activity of imipenem against The bactericidal activity of drug combinations was assayed in broth and in human macrophages. The efficacy of the drugs was tested by monitoring the survival of infected zebrafish embryos.

Factors essential for L,D-transpeptidase-mediated peptidoglycan cross-linking and β-lactam resistance in .

The target of β-lactam antibiotics is the D,D-transpeptidase activity of penicillin-binding proteins (PBPs) for synthesis of 4→3 cross-links in the peptidoglycan of bacterial cell walls. Unusual 3→3 cross-links formed by L,D-transpeptidases were first detected in more than four decades ago, however no phenotype has previously been associated with their synthesis. Here we show that production of the L,D-transpeptidase YcbB in combination with elevated synthesis of the (p)ppGpp alarmone by RelA lead to full bypass of the D,D-transpeptidase activity of PBPs and to broad-spectrum β-lactam resistance.

Peptidoglycan cross-linking in glycopeptide-resistant Actinomycetales.

Synthesis of peptidoglycan precursors ending in D-lactate (D-Lac) is thought to be responsible for glycopeptide resistance in members of the order Actinomycetales that produce these drugs and in related soil bacteria. More recently, the peptidoglycan of several members of the order Actinomycetales was shown to be cross-linked by L,D-transpeptidases that use tetrapeptide acyl donors devoid of the target of glycopeptides. To evaluate the contribution of these resistance mechanisms, we have determined the peptidoglycan structure of Streptomyces coelicolor A(3)2, which harbors a vanHAX gene cluster for the production of precursors ending in D-Lac, and Nonomuraea sp.

Inactivation kinetics of a new target of beta-lactam antibiotics.

Peptidoglycan is predominantly cross-linked by serine DD-transpeptidases in most bacterial species. The enzymes are the essential targets of β-lactam antibiotics. However, unrelated cysteine LD-transpeptidases have been recently recognized as a predominant mode of peptidoglycan cross-linking in Mycobacterium tuberculosis and as a bypass mechanism conferring resistance to all β-lactams, except carbapenems such as imipenem, in Enterococcus faecium.

Differential modulation of TNF-alpha-induced apoptosis by Neisseria meningitidis.

Infections by Neisseria meningitidis show duality between frequent asymptomatic carriage and occasional life-threatening disease. Bacterial and host factors involved in this balance are not fully understood. Cytopathic effects and cell damage may prelude to pathogenesis of isolates belonging to hyper-invasive lineages.