Resistance to beta-lactams and quinolones in two isogenic Enterobacter cloacae isolates was studied. One was susceptible to cefoxitin and amoxicillin-clavulanate. The other one showed its natural beta-lactam resistance pattern. Both isolates had a nonfunctional AmpR regulator. However, within the second one, the presence of a plasmid carrying ampR and qnrA1 allowed reversion to the wild-type be...

II. The occurrence of modified penicillin-binding sites Modified PBPs have a lower affinity for β-lactam antibiotics, requiring clinically unattainable concentrations of the drug to effect its bactericidal activity Example: penicillin resistance in Streptococcus pneumoniae (pneumococcus) is caused by altered PBPs I. Production of β-lactamases This family of enzymes can inactivate penicillins by...

The prevalence of antibiotic resistance genes in pathogenic bacteria is a major challenge to treating many infectious diseases. The spread of these genes is driven by the strong selection imposed by the use of antibacterial drugs. However, in the absence of drug selection, antibiotic resistance genes impose a fitness cost, which can be ameliorated by compensatory mutations. In Streptococcus pne...

Definitions: Beta-lactam antimicrobials are characterized by having a four-membered cyclic amide (beta-lactam ring) as part of their chemical structure (Figure 1) [1]. This broad group includes the penicillins, cephalosporins, carbapenems, and monobactams [1]. All beta-lactams have a similar mechanism of action; they inhibit bacterial cell wall synthesis [1]. Resistance to beta-lactam antimicro...

The SOS response, a conserved regulatory network in bacteria that is induced in response to DNA damage, has been shown to be associated with the emergence of resistance to antibiotics. Previously, we demonstrated that heterogeneous (HeR) MRSA strains, when exposed to sub-inhibitory concentrations of oxacillin, were able to express a homogeneous high level of resistance (HoR). Moreover, we showe...

The blanket resistance of methicillin-resistant Staphylococcus aureus to all beta-lactam antibiotics--which had such a devastating impact on chemotherapy of staphylococcal infections--is related to the properties of the key component of this resistance mechanism: the "acquired" penicillin-binding protein (PBP)-2A, which has unusual low affinity for all beta-lactam antibiotics. Until now, the ac...

The NDM-1 gene, first identified in Sweden in 2008 in Klebsiella pneumoniae from a patient hospitalized in New Delhi, encodes a metallo-β-lactamase that inactivates all β-lactams except aztreonam. This bla(NDM-1) gene has been identified in hospital-acquired bacterial species, such as K. pneumoniae, but also in the typical community-acquired species, Escherichia coli. This gene has been identif...

It has long been recognized that the modification of penicillin-binding proteins (PBPs) to reduce their affinity for beta-lactams is an important mechanism (target modification) by which Gram-positive cocci acquire antibiotic resistance. Among Gram-negative rods (GNR), however, this mechanism has been considered unusual, and restricted to clinically irrelevant laboratory mutants for most specie...

OBJECTIVES plasmid pB1000 bearing bla(ROB-1) is responsible for high-level β-lactam resistance in Haemophilus influenzae as well as in Pasteurella multocida and Haemophilus parasuis isolates from Spain. Here, we explore the presence of ROB-1 in Italy and investigate the relative contribution of penicillin-binding protein 3 (PBP3) mutations and ROB-1 to the β-lactam resistance phenotype in H. in...

Bacterial resistance to standard (i.e., β-lactam-based) antibiotics has become a global pandemic. Simultaneously, research into the underlying causes of resistance has slowed substantially, although its importance is universally recognized. Key to unraveling critical details is characterization of the noncovalent interactions that govern binding and specificity (DD-peptidases, antibiotic target...