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Cureus Aug 2023Lyme disease and its treatment implications have become an ever-increasing area of concern within the United States related to the markedly increased prevalence of... (Review)
Review
Lyme disease and its treatment implications have become an ever-increasing area of concern within the United States related to the markedly increased prevalence of infection within the last two decades. The presentation, pathophysiology, and epidemiology of Lyme disease have been well studied, and thus treatments for this disease are widely available. While the treatment of its early and late stages is relatively simple with 10-14 day and four-week courses of doxycycline, respectively, the main problem rests in the understanding of the etiology and pathology of post-treatment Lyme disease syndrome (PTLDS). With the time of symptoms onsetting approximately six months after treatment and potentially lasting indefinitely, this syndrome's effect on patients' quality of life could be devastating. Searching on PubMed, Google Scholar, MEDLINE, and ScienceDirect using keywords including Lyme disease, PTLDS, doxycycline, erythema migrans, azlocillin, and treatment, the authors have tried to make clear the different aspects. The authors have reviewed and discussed clinical studies of Lyme disease and its treatments/potential therapeutics as well as PTLDS and its sparse treatments/potential therapeutics.
PubMed: 37692614
DOI: 10.7759/cureus.43112 -
Journal of Biomolecular Structure &... Oct 2023Antimicrobial resistance poses a significant challenge to public health, especially in developing countries, due to a substantial rise in bacterial resistance. This...
Antimicrobial resistance poses a significant challenge to public health, especially in developing countries, due to a substantial rise in bacterial resistance. This situation has become so concerning that we are now at risk of losing the effectiveness of antibiotics altogether. Recent research has firmly established that bacteria engage in a process called quorum sensing (QS). QS regulates various functions, including nutrient scavenging, immune response suppression, increased virulence, biofilm formation and mobility. , an opportunistic bacterial pathogen, plays a significant role in various medical conditions such as chronic wounds, corneal infections, burn wounds and cystic fibrosis. While antibiotics are effective in killing bacteria, only a few antibiotics, particularly those from the β-lactam group, have been studied for their impact on the quorum sensing of . Given the lack of concentrated efforts in this area, we have investigated the role of β-lactam antibiotics on various potential targets of . Based on their toxicological profiles and the average binding energy obtained through molecular docking, azlocillin and moxalactam have emerged as lead antibiotics. The binding energy for the docking of azlocillin and moxalactam with LasA was determined to be -8.2 and -8.6 kcal/mol, respectively. Molecular simulation analysis has confirmed the stable interaction of both these ligands with all three target proteins (LasI, LasA and PqsR) under physiological conditions. The results of this research underscore the effectiveness of azlocillin and moxalactam. These two antibiotics may be repurposed to target the quorum sensing of .Communicated by Ramaswamy H. Sarma.
PubMed: 37904338
DOI: 10.1080/07391102.2023.2275181 -
ACS Infectious Diseases Apr 2024Effective treatment of gonorrhea is threatened by the increasing prevalence of strains resistant to the extended-spectrum cephalosporins (ESCs). Recently, we...
Effective treatment of gonorrhea is threatened by the increasing prevalence of strains resistant to the extended-spectrum cephalosporins (ESCs). Recently, we demonstrated the promise of the third-generation cephalosporin cefoperazone as an antigonococcal agent due to its rapid second-order rate of acylation against penicillin-binding protein 2 (PBP2) from the ESC-resistant strain H041 and robust antimicrobial activity against H041. Noting the presence of a ureido moiety in cefoperazone, we evaluated a subset of structurally similar ureido β-lactams, including piperacillin, azlocillin, and mezlocillin, for activity against PBP2 from H041 using biochemical and structural analyses. We found that the ureidopenicillin piperacillin has a second-order rate of acylation against PBP2 that is 12-fold higher than cefoperazone and 85-fold higher than ceftriaxone and a lower MIC against H041 than ceftriaxone. Surprisingly, the affinity of ureidopenicillins for PBP2 is minimal, indicating that their inhibitory potency is due to a higher rate of the acylation step of the reaction compared to cephalosporins. Enhanced acylation results from the combination of a penam scaffold with a 2,3-dioxopiperazine-containing R group. Crystal structures show that the ureido β-lactams overcome the effects of resistance mutations present in PBP2 from H041 by eliciting conformational changes that are hindered when PBP2 interacts with the weaker inhibitor ceftriaxone. Overall, our results support the potential of piperacillin as a treatment for gonorrhea and provide a framework for the future design of β-lactams with improved activity against ESC-resistant .
Topics: Humans; Ceftriaxone; Neisseria gonorrhoeae; Gonorrhea; Penicillin-Binding Proteins; Cefoperazone; Cephalosporins; Piperacillin; beta-Lactams
PubMed: 38446051
DOI: 10.1021/acsinfecdis.3c00713