scholarly journals Screening transposon-mutant library of methicillin-resistant Staphylococcus aureus for mutants with altered sensitivity toward three antimicrobial agents

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Mahmoud Ahmed ◽  
George Beshara ◽  
Bryan Ubanwa ◽  
Taeok Bae
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Mutant Library ◽  
Beta Lactam ◽  
Methicillin Resistant ◽  
Beta Lactam Antibiotics ◽  
Transposon Mutants ◽  
Almost All ◽  
Altered Sensitivity

Background and Hypothesis: Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to almost all beta-lactam antibiotics, including oxacillin. To combat MRSA infections, recently, new classes of drugs are developed, such as oxadiazole DR1 and ESP404. We hypothesize that, if we identify MRSA mutants with altered sensitivity toward the drugs, those mutants will help us understand the antimicrobial mechanisms of the drugs. Experimental Design or Project Methods: The screening was carried out on the Nebraska library consisting of 1,920 non-redundant transposon mutants of USA300 strain in 96 well plates. First, the minimum inhibitory concentration (MIC) of each drug was determined. Then the transposon mutants were grown in tryptic soy broth (TSB) containing either 1/4× MIC or 4× MIC of the drugs for sensitive mutants and resistant mutants respectively. Due to the limited availability of ESP404, the drug was used to screen for sensitive mutants only. Results: The first screening identified 81 mutants with altered drug sensitivity: 23 for oxadiazole DR1 (5 sensitive, 18 resistant); 20 for ESP404 (all sensitive); 38 for oxacillin (18 sensitive, 5 resistant). Conclusion and Potential Impact: Screening of the transposon-mutant library identified multiple mutants that have altered sensitivity toward three drugs against S. aureus. Further verification of the phenotype and characterization of those mutants are expected to shed light on the antimicrobial mechanism of the drugs and open a door for the development of drug-potentiators.

Genomic Overview into the Evolving Epidemiology of Methicillin-Resistant Staphylococcus aureus

2020 ◽  
Vol 21 (3) ◽  
pp. 125-131
Author(s):  
Yara El dessouky ◽  
Shaimaa Mouftah ◽  
Mohamed Elhadidy
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Human Infection ◽  
Emerging Infections ◽  
Beta Lactam ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Beta Lactam Antibiotics ◽  
Mrsa Strains ◽  
Hospital Acquired

Emerging infections represent an enormous challenge to both human and veterinary medicine. Identification of Methicillin-Resistant Staphylococcus aureus (MRSA) in various species and in food has raised concerns about the roles of animals in the epidemiology of MRSA. MRSA are a group of gram-positive bacteria, distinct from other strains of S. aureus in that this pathogen is resistant to methicillin, oxacillin, and all beta-lactam antibiotics. The severity of infections caused by MRSA depends on the strain responsible for the infection and can vary from soft tissue infections to bacteremia and sometimes pneumonia. MRSA strains are divided into clones, based on their genetic makeup. According to the setting of infection, MRSA are divided into three epidemiological types: hospital acquired (HA-MRSA), community acquired (CA-MRSA), and livestock acquired (LA-MRSA) (ie. Transmitted from animal carriers). The epidemiology of HA-MRSA, CA-MRSA, and LA-MRSA is blurred as different recent genetic studies have revealed significant overlap of identical clones between HA-MRSA and CA-MRSA, and the significant increase of human infection caused by LA-MRSA. Furthermore, the animal-human and animal-animal transmission of LA-MRSA has prompted further investigation to study the origin of this epidemiological type and the transmission dynamics. The genetic and virulence profiles of different types of MRSA vary widely, where community acquired and livestock acquired strains are more virulent than hospital acquired strains. This review sheds light on three epidemiological groups of MRSA (HA-MRSA, CA-MRSA, and LA-MRSA), and their most prevalent clonal clusters, that can consequently allow better understanding of their evolution, emergence, transmission, and global dissemination.

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