Beta-lactam antibiotics: from antibiosis to resistance and bacteriology

This review focuses on the era of antibiosis that led to a better understanding of bacterial morphology, in particlar the cell wall component peptidoglycan. This is an effort to take readers on a tour de force from the concept of antibiosis, to the serepidity of antibiotics, evolution of betalactam development, and the molecular biology of antibiotic resistance. These areas of research have culminated in a deeper understanding of microbiology, particularly in the area of bacterial cell wall synthesis and recycling. In spite of this knowledge, which has enabled design of new even more effective therapeutics to combat bacterial infection and has provided new research tools, antibiotic resistance remains a worldwide health care problem

An Analysis of Why Highly Similar Enzymes Evolve Differently

Abstract The TEM-1 and SHV-1 β-lactamases are important contributors to resistance to β-lactam antibiotics in gram-negative bacteria. These enzymes share 68% amino acid sequence identity and their atomic structures are nearly superimposable. Extended-spectrum cephalosporins were introduced to avoid the action of these β-lactamases. The widespread use of antibiotics has led to the evolution of variant TEM and SHV enzymes that can hydrolyze extended-spectrum antibiotics. Despite being highly similar in structure, the TEM and SHV enzymes have evolved differently in response to the selective pressure of antibiotic therapy. Examples of this are at residues Arg164 and Asp179. Among TEM variants, substitutions are found only at position 164, while among SHV variants, substitutions are found only at position 179. To explain this observation, the effects of substitutions at position 164 in both TEM-1 and SHV-1 on antibiotic resistance and on enzyme catalytic efficiency were examined. Competition experiments were performed between mutants to understand why certain substitutions preferentially evolve in response to the selective pressure of antibiotic therapy. The data presented here indicate that substitutions at position Asp179 in SHV-1 and Arg164 in TEM-1 are more beneficial to bacteria because they provide increased fitness relative to either wild type or other mutants.</jats:p

Amino Acid Residues That Contribute to Substrate Specificity of Class A β-Lactamase SME-1

Carbapenem antibiotics are used as antibiotics of last resort because they possess a broad spectrum of antimicrobial activity and are not easily hydrolyzed by β-lactamases. Recently, class A enzymes, such as the SME-1, NMC-A, and IMI-1 β-lactamases, have been identified with the capacity to hydrolyze carbapenem antibiotics. Traditional class A β-lactamases, such as TEM-1 and SHV-1, are unable to hydrolyze carbapenem antibiotics and exhibit some differences in sequence from those that are able to hydrolyze carbapenem antibiotics. The positions that differ may contribute to the unique substrate specificity of the class A carbapenemase SME-1. Codons in the SME-1 gene representing residues 104, 105, 132, 167, 237, and 241 were randomized by site-directed mutagenesis, and functional mutants were selected for the ability to hydrolyze imipenem, ampicillin, or cefotaxime. Although several positions are important for hydrolysis of β-lactam antibiotics, no single position was found to uniquely contribute to carbapenem hydrolysis. The results of this study support a model whereby the carbapenemase activity of SME-1 is due to a highly distributed set of interactions that subtly alter the structure of the active-site pocket

Amino Acid Sequence Requirements at Residues 69 and 238 for the SME-1 β-Lactamase To Confer Resistance to β-Lactam Antibiotics

Carbapenem antibiotics have been used to counteract resistant strains of bacteria harboring β-lactamases and extended-spectrum β-lactamases. Four enzymes from the class A group of β-lactamases, NMC-A, IMI-1, SME-1, and KPC-1, efficiently hydrolyze carbapenem antibiotics. Sequence comparisons and structural information indicate that cysteines at amino acid residues 69 and 238, which are conserved in all four of these enzymes, form a disulfide bond that is unique to these β-lactamases. To test whether this disulfide bond is required for catalytic activity, the codons for residues Cys69 and Cys238 were randomized individually and simultaneously by PCR-based mutagenesis to create random replacement libraries for these positions. Mutants that were able to confer resistance to ampicillin, imipenem, or cefotaxime were selected from these libraries. The results indicate that positions Cys69 and Cys238 are critical for hydrolysis of all of the antibiotics tested, suggesting that the disulfide bond is generally required for this enzyme to catalyze the hydrolysis of β-lactam antibiotics

Language's Borrowings: The Role of the Borrowed and Arabized Words in Enriching Arabic Language

<p>Borrowing is entering Arabic language. Researchers focus on the origin of the borrowed words and their meanings without analyzing the syntactic and semantic changes of these words. This paper focuses on Arabic language's borrowings from other languages. Moreover, it studies the meaning of 'arabization' and the role of arabized and borrowed words in enriching Arabic language, the difference between the arabized words and the borrowed ('<em>dakheel</em>') ones by examining and analyzing samples for every type. Arabic words are derivatives from the base form, which is applied to "<em>wazen</em>", three-letter, '<em>fa</em>', '<em>'a</em>", and '<em>la</em>', three-syllable and three-sound word.  The words, which will be studied, are used among speakers of Arabic,  and have equivalents in Arabic, besides they follow Arabic rules in a variety of methods, syntactically, morphologically and phonetically.  In the process of arabization, these words show that a change happens by an addition of a letter, deletion or replacement of a letter, or by a change in the manner of articulation. Moreover, they exist in more than one phonetic form which permits Arabic language to adopt one of these forms and arabize it.</p><p> </p

Al Qomus al Muhit

503 Hal.; 23 C

Mu jam a-qamus al-muhith : murattab tartiban alifaba iyan wafq awa il al-huruf/ Fayruz Abadiy

1437 hal.; 25 cm