Photoacoustic discrimination of antibiotic‐resistant and sensitive Staphylococcus aureus isolates

2021 ◽  
Author(s):  
Robert H. Edgar ◽  
Anie‐Pier Samson ◽  
Justin Cook ◽  
Madeline Douglas ◽  
Ken Urish ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Resistant

Systematic analysis and integrative discovery of active-site subpocket-specific dehydroquinate synthase inhibitors combating antibiotic-resistant Staphylococcus aureus infection

2018 ◽  
Vol 16 (06) ◽  
pp. 1850027
Author(s):  
Quanfeng Liu ◽  
Liping Li ◽  
Fei Xu
Keyword(s):  
Staphylococcus Aureus ◽  
Active Site ◽  
Shikimate Pathway ◽  
In Vitro Susceptibility ◽  
Systematic Analysis ◽  
Antibiotic Resistant ◽  
Enzyme Active Site ◽  
Specific Inhibitors ◽  
Dehydroquinate Synthase

Shikimate pathway plays an essential role in the biosynthesis of aromatic amino acids in various plants and bacteria, which consists of seven key enzymes and they are all attractive targets for antibacterial agent development due to their absence in humans. The Staphylococcus aureus dehydroquinate synthase (SaDHQS) is involved in the second step of shikimate pathway, which catalyzes the NAD[Formula: see text]-dependent conversion of 3-deoxy-D-arabino-heptulosonate-7-phosphate to dehydroquinate via multiple steps. The enzyme active site can be characterized by two spatially separated subpockets 1 and 2, which represent the reaction center of substrate adduct with NAD[Formula: see text] nicotinamide moiety and the assistant binding site of NAD[Formula: see text] adenine moiety, respectively. In silico virtual screening is performed against a biogenic compound library to discover SaDHQS subpocket-specific inhibitors, which were then tested against both antibiotic-sensitive and antibiotic-resistant S. aureus strains by using in vitro susceptibility test. The activity profile of hit compounds has no considerable difference between the antibiotic-sensitive and -resistant strains. The subpocket 1-specific inhibitors exhibit a generally higher activity than subpocket 2-specific inhibitors, and they also hold a strong selectivity between their cognate and noncognate subpockets. Dynamics and energetics analyses reveal that the SaDHQS active site prefers to interact with amphipathic and polar inhibitors by forming multiple hydrogen bonds and van der Waals packing at the complex interfaces of the two subpockets with their cognate inhibitors.

scholarly journals Quantifying the Exposure to Antibiotic-Resistant Pathogens Among Patients Discharged From a Single Hospital Across All California Healthcare Facilities

2015 ◽  
Vol 36 (11) ◽  
pp. 1275-1282 ◽  
Author(s):  
Rupak Datta ◽  
Shawn Brown ◽  
Vinh Q. Nguyen ◽  
Chenghua Cao ◽  
John Billimek ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Nursing Homes ◽  
Hospital Readmissions ◽  
Time Dependent ◽  
Antibiotic Resistant ◽  
Total Exposure ◽  
Healthcare Facilities ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant

OBJECTIVETo assess the time-dependent exposure of California healthcare facilities to patients harboring methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), extended-spectrum β-lactamase (ESBL)–producing Escherichia coli and Klebsiella pneumoniae, and Clostridium difficile infection (CDI) upon discharge from 1 hospital.METHODSRetrospective multiple-cohort study of adults discharged from 1 hospital in 2005–2009, counting hospitals, nursing homes, cities, and counties in which carriers were readmitted, and comparing the number and length of stay of readmissions and the number of distinct readmission facilities among carriers versus noncarriers.RESULTSWe evaluated 45,772 inpatients including those with MRSA (N=1,198), VRE (N=547), ESBL (N=121), and CDI (N=300). Within 1 year of discharge, MRSA, VRE, and ESBL carriers exposed 137, 117, and 45 hospitals and 103, 83, and 37 nursing homes, generating 58,804, 33,486, and 15,508 total exposure-days, respectively. Within 90 days of discharge, CDI patients exposed 36 hospitals and 35 nursing homes, generating 7,318 total exposure-days. Compared with noncarriers, carriers had more readmissions to hospitals (MRSA:1.8 vs 0.9/patient; VRE: 2.6 vs 0.9; ESBL: 2.3 vs 0.9; CDI: 0.8 vs 0.4; all P<.001) and nursing homes (MRSA: 0.4 vs 0.1/patient; VRE: 0.7 vs 0.1; ESBL: 0.7 vs 0.1; CDI: 0.3 vs 0.1; all P<.001) and longer hospital readmissions (MRSA: 8.9 vs 7.3 days; VRE: 8.9 vs 7.4; ESBL: 9.6 vs 7.5; CDI: 12.3 vs 8.2; all P<.01).CONCLUSIONSPatients harboring antibiotic-resistant pathogens rapidly expose numerous facilities during readmissions; regional containment strategies are needed.Infect. Control Hosp. Epidemiol. 2015;36(11):1275–1282

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