Bacterial cell wall nature and its mode of resistance against antibiotic drugs: An Overview (original) (raw)
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Suppression of the Lytic and Bactericidal Effects of Cell Wall-Inhibitory Antibiotics
Antimicrobial Agents and Chemotherapy, 1976
MATERIALS AND METHODS Bacterial strains. Two bacterial strains were used: Streptococcus pneumoniae strain R36A (Rockefeller University laboratory stock) and B. subtilis 168 (obtained from Leonard Mindich of the Public Health Research Institute, New York, N.Y.). Antibiotics. Amidino penicillin FL 1060 (mecillinam) was obtained from Leo Co., Ballerup, Denmark. D-Cycloserine (Merck) and benzylpenicillin (Squibb) were commercial products; sodium dicloxacillin was obtained from Wyeth Labs, Inc., Philadelphia, Pa.; cephalothin was a gift of Kenneth Price of Bristol Laboratories, Syracuse, N.Y.; and betachloro-n-alanine was kindly supplied by James Manning of The Rockefeller University, New York, N.Y. Trypsin (2x recrystallized, Worthington Biochemicals Corp., Freehold, N.J.) and all other reagents and medium components were reagentgrade, commercially available products. Growth media. A synthetic medium containing
BMC Microbiology, 2011
Background Antibiotics which inhibit bacterial peptidoglycan biosynthesis are the most widely used in current clinical practice. Nevertheless, resistant strains increase dramatically, with serious economic impact and effects on public health, and are responsible for thousands of deaths each year. Critical clinical situations should benefit from a rapid procedure to evaluate the sensitivity or resistance to antibiotics that act at the cell wall. We have adapted a kit for rapid determination of bacterial DNA fragmentation, to assess cell wall integrity. Results Cells incubated with the antibiotic were embedded in an agarose microgel on a slide, incubated in an adapted lysis buffer, stained with a DNA fluorochrome, SYBR Gold and observed under fluorescence microscopy. The lysis affects the cells differentially, depending on the integrity of the wall. If the bacterium is susceptible to the antibiotic, the weakened cell wall is affected by the lysing solution so the nucleoid of DNA conta...
PNAS, 2021
Bacterial cell wall peptidoglycan is essential, maintaining both cel- lular integrity and morphology, in the face of internal turgor pres- sure. Peptidoglycan synthesis is important, as it is targeted by cell wall antibiotics, including methicillin and vancomycin. Here, we have used the major human pathogen Staphylococcus aureus to elucidate both the cell wall dynamic processes essential for growth (life) and the bactericidal effects of cell wall antibiotics (death) based on the principle of coordinated peptidoglycan synthesis and hydrolysis. The death of S. aureus due to depletion of the essen- tial, two-component and positive regulatory system for peptido- glycan hydrolase activity (WalKR) is prevented by addition of otherwise bactericidal cell wall antibiotics, resulting in stasis. In contrast, cell wall antibiotics kill via the activity of peptidoglycan hydrolases in the absence of concomitant synthesis. Both methicil- lin and vancomycin treatment lead to the appearance of perforat- ing holes throughout the cell wall due to peptidoglycan hydrolases. Methicillin alone also results in plasmolysis and mis- shapen septa with the involvement of the major peptidoglycan hydrolase Atl, a process that is inhibited by vancomycin. The bacte- ricidal effect of vancomycin involves the peptidoglycan hydrolase SagB. In the presence of cell wall antibiotics, the inhibition of pep- tidoglycan hydrolase activity using the inhibitor complestatin results in reduced killing, while, conversely, the deregulation of hydrolase activity via loss of wall teichoic acids increases the death rate. For S. aureus, the independent regulation of cell wall synthe- sis and hydrolysis can lead to cell growth, death, or stasis, with implications for the development of new control regimes for this important pathogen.
The bacterial cell-wall that forms a protective layer over the inner membrane is called the murein sacculus – a tightly cross-linked peptidoglycan mesh unique to bacteria. Cell-wall synthesis and recycling are critical cellular processes essential for cell growth, elongation and division. Both de novo synthesis and recycling involve an array of enzymes across all cellular compartments, namely the outer membrane, periplasm, inner membrane and cytoplasm. Due to the exclusivity of peptidoglycan in the bacterial cell-wall, these players are the target of choice for many antibacterial agents. Our current understanding of cell-wall biochemistry and biogenesis in Gram-negative organisms stems mostly from studies of Escherichia coli. An incomplete knowledge on these processes exists for the opportunistic Gram-negative pathogen, Pseudomonas aeruginosa. In this review, cell-wall synthesis and recycling in the various cellular compartments are compared and contrasted between E. coli and P. aeruginosa. Despite the fact that there is a remarkable similarity of these processes between the two bacterial species, crucial differences alter their resistance to b-lactams, fluoroquinolones and aminoglycosides. One of the common mediators underlying resistance is the amp system whose mechanism of action is closely associated with the cell-wall recycling pathway. The activation of amp genes results in expression of AmpC b-lactamase through its cognate regulator AmpR which further regulates multi-drug resistance. In addition, other cell-wall recycling enzymes also contribute to antibiotic resistance. This comprehensive summary of the information should spawn new ideas on how to effectively target cell-wall processes to combat the growing resistance to existing antibiotics.
Antibiotic Resistance Mechanisms of Clinically Important Bacteria
Medicina, 2011
Bacterial resistance to antimicrobial drugs is an increasing health and economic problem. Bacteria may be innate resistant or acquire resistance to one or few classes of antimicrobial agents. Acquired resistance arises from: (i) mutations in cell genes (chromosomal mutation) leading to cross-resistance, (ii) gene transfer from one microorganism to other by plasmids (conjugation or transformation), transposons (conjugation), integrons and bacteriophages (transduction). After a bacterium gains resistance genes to protect itself from various antimicrobial agents, bacteria can use several biochemical types of resistance mechanisms: antibiotic inactivation (interference with cell wall synthesis, e.g., β-lactams and glycopeptide), target modification (inhibition of protein synthesis, e.g., macrolides and tetracyclines; interference with nucleic acid synthesis, e.g., fluoroquinolones and rifampin), altered permeability (changes in outer membrane, e.g., aminoglycosides; new membrane transpo...
Lactam Resistance in Staphylococcus aureus Cells That Do Not Require a Cell Wall for Integrity
Antimicrobial Agents and Chemotherapy, 2005
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Journal of Antimicrobial Chemotherapy, 2013
Tolerance refers to the phenomenon that bacteria do not significantly die when exposed to bactericidal antibiotics. Enterococci are known for their high tolerance to these drugs, but the molecular reasons why they resist killing are not understood. In a previous study we showed that the superoxide dismutase (SOD) is implicated in this tolerance. This conclusion was based on the results obtained with one particular strain of Enterococcus faecalis and therefore the objective of the present communication was to analyse whether dependence of tolerance on active SOD is a general phenomenon for enterococci and another Gram-positive pathogen, Staphylococcus aureus. Methods: Mutants deficient in SOD activity were constructed in pathogenic enterococci. The wild-type sodA gene was cloned into an expression vector and transformed into SOD-deficient strains for complementation with varying levels of SOD activity. Previously constructed SOD-deficient strains of S. aureus were also included in this study. Tolerance to vancomycin and penicillin was then tested. Results: We demonstrated that the dependence on SOD of tolerance to vancomycin and penicillin is a common trait of antibiotic-susceptible pathogenic enterococci. By varying the levels of expression we could also show that tolerance to vancomycin is directly correlated to SOD activity. Interestingly, deletion of the sodA gene in a nontolerant Enterococcus faecium strain did not further sensitize the mutant to bactericidal antibiotics. Finally, we showed that the SOD enzymes of S. aureus are also implicated in tolerance to vancomycin. Conclusion: High tolerance of enterococci to cell wall active antibiotics can be reversed by SOD deficiency.
Cell-Wall Recycling of the Gram-Negative Bacteria and the Nexus to Antibiotic Resistance
Chemical Reviews, 2018
The importance of the cell wall to the viability of the bacterium is underscored by the breadth of antibiotic structures that act by blocking key enzymes that are tasked with cell-wall creation, preservation, and regulation. The interplay between cell-wall integrity, and the summoning forth of resistance mechanisms to deactivate cell-wall-targeting antibiotics, involves exquisite orchestration among cell-wall synthesis and remodeling and the detection of and response to the antibiotics through modulation of gene regulation by specific effectors. Given the profound importance of antibiotics to the practice of medicine, the assertion that understanding this interplay is among the most fundamentally important questions in bacterial physiology is credible. The enigmatic regulation of the expression of the AmpC β-lactamase, a clinically significant and highly regulated resistance response of certain Gram-negative bacteria to the β-lactam antibiotics, is the exemplar of this challenge. This review gives a current perspective to this compelling, and still not fully solved, 35-year enigma.