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A Themed Issue in Honor of Professor Alexander Tomasz—Outstanding Contributions...
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A Themed Issue in Honor of Professor Alexander Tomasz—Outstanding Contributions in the Fields of Antibiotic Resistance and Bacterial Infectious Diseases

A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 34837

Special Issue Editor

Prof. Dr. Choon Kim

E-Mail Website
Guest Editor
Department of Chemistry and Biochemistry, University of Notre Dame, 352C McCourtney Hall, Notre Dame, IN 46556, USA
Interests: MRSA; MDR pathogens; beta-lactamases; antibiotic resistance; antibiotic adjuvants; drug discovery; cell-wall recycling in Gram-negative bacteria

Special Issue Information

Dear Colleagues,

Professor Dr. Alexander Tomasz has significantly contributed to the fields of antibiotic resistance and bacterial infectious diseases. His major areas of research include penicillin-binding proteins (PBPs) of Streptococcus pneumoniae and Staphylococcus aureus, and the mechanisms of antibiotic resistance and virulence in multidrug-resistant pneumococci, staphylococci and enterococci, as well as molecular epidemiology of drug-resistant clones. In 1965, he discovered that pneumococci excrete a modified polypeptide that allows foreign DNA to pass through cell walls. This finding has been cited as the first evidence that bacteria “talk” to one another, a concept later called quorum sensing. He also discovered a mechanism named antibiotic tolerance, which enables bacterial cells to evade the programmed cell death triggered by antibiotics. Professor Tomasz was the first scientist to demonstrate that penicillin resistance in S. pneumoniae involves the reengineering of PBPs using blocks of foreign DNA that reduce the affinity of PBPs to the antibiotic. Pneumococci with the reengineered “mosaic” PBPs are not only resistant to penicillin but also show an altered chemical structure of their cell walls. Professor Tomasz has also focused on the role of the cell wall in bacterial virulence and antibiotic resistance. His research led to the identification of specific mutations in an yvqF-vraSR operon that accompanied the evolution of antibiotic resistance in a S. aureus strain from a patient undergoing extensive chemotherapy by vancomycin and evolution from vancomycin-susceptible S. aureus (VSSA) to vancomycin-intermediate S. aureus (VISA). Prof. Tomasz’s lab has tracked the spread of antibiotic-resistant clones of staphylococci, pneumococci and enterococci in hospitals and community health centers, mostly in collaboration with laboratories in Europe, South America and the USA, in order to identify rapidly the resistance mechanisms of newly emerged drug-resistant strains.

Professor Tomasz was born in Budapest, Hungary and escaped to the US in 1956 after the Soviet invasion of Hungary. He received his Ph.D. in biochemistry from Columbia University in 1963. He spent a year as a postdoctoral fellow at the Rockefeller University. He became assistant professor at the Rockefeller University in 1964, associate professor in 1967, professor in 1973, and professor emeritus in 2019. In 1982, Professor Tomasz was the first recipient of the Hoechst-Roussel Award of the American Society for Microbiology, and he received the Selman A. Waksman Award in 1987. He published about 450 papers including original research, reviews and chapters in books. Professor Tomasz was co-founder and chairperson of a Gordon Research Conference on Bacterial Cell Surfaces in 1970. He was also co-founder and director of Bacterial Antibiotic Resistance Initiative, NYC in 1994 and was director and co-founder of the CEM/NET (Center for Molecular Epidemiology and Network for Epidemiological Tracking of Antibiotic Resistant Pathogens) established in 1995.  The CEM-NET initiative represents the chronologically first organized international effort in molecular epidemiology of drug-resistant staphylococci and pneumococci.

Professor Tomasz served as a member of Board of Reviewers for the Journal of Bacteriology, Infection and Immunity, Journal of Virology, Antimicrobial Agents and Chemotherapy among others.  He also served as a member of the Editorial Board of Journal of Bacteriology, Antimicrobial Agents and Chemotherapy and Journal of Infectious Diseases. He was Editor-in Chief of Microbial Drug Resistance from 1995 to 2020. He has been a grant reviewer for the NIH and NSF for many years.

Antibiotics is pleased to announce a Special Issue honoring Professor Alexander Tomasz for his outstanding contributions to mechanisms of antibiotic resistance in bacterial pathogens. This Special Issue is dedicated to all aspects of antibiotic resistance in the following topics, but not limited to:

  1. Advances in streptococcal or staphylococcal drug resistance
  2. Advances in antibiotic resistance of Gram-negative bacteria
  3. Advances in β-lactamases and their inhibitors
  4. Penicillin-binding proteins and β-lactam resistance
  5. Novel antimicrobial agents against multidrug-resistant pathogens
  6. Molecular epidemiology of antibiotic resistance
  7. Bacterial infections during COVID-19

We are pleased to invite you to submit a manuscript to this Special Issue; regular articles, communications and reviews are all welcome.

Prof. Dr. Choon Kim
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • MRSA
  • VRSA
  • MDR
  • PBP
  • COVID-19
  • Antibiotic Resistance
  • Antibiotic Tolerance
  • Molecular Epidemiology
  • Bacterial Infections
  • β-lactamases
  • Novel Antimicrobials
  • Virulence

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Published Papers (10 papers)

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Research

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10 pages, 586 KiB  
Article
Retrospective Comparison of the Effectiveness and Safety of Ceftriaxone 1 g Twice Daily versus 2 g Once Daily for Treatment of Aspiration Pneumonia
by Hideo Kato, Mao Hagihara, Yoshihiko Morikawa, Nobuhiro Asai, Hiroshige Mikamo and Takuya Iwamoto
Antibiotics 2022, 11(8), 983; https://doi.org/10.3390/antibiotics11080983 - 22 Jul 2022
Cited by 4 | Viewed by 3808
Abstract
Although a 2 g once daily administration of ceftriaxone remains the standard dosing regimen for the treatment of aspiration pneumonia, there are no studies to investigate the optimal dosing method. Hence, we retrospectively evaluated the effectiveness and safety of 1 g twice daily [...] Read more.
Although a 2 g once daily administration of ceftriaxone remains the standard dosing regimen for the treatment of aspiration pneumonia, there are no studies to investigate the optimal dosing method. Hence, we retrospectively evaluated the effectiveness and safety of 1 g twice daily versus 2 g once daily administration of ceftriaxone in adult patients with aspiration pneumonia. Patients who received ceftriaxone for the treatment of aspiration pneumonia between 2015 and 2021 were included in this study. Clinical responses, inflammatory markers, and incidence of adverse events after completion of ceftriaxone therapy were investigated. In total, 33 patients received 1 g twice daily (group 1) and 28 received 2 g once daily (group 2) ceftriaxone for the treatment of mild-to-moderate aspiration pneumonia. Compared with that of group 1, group 2 demonstrated significantly improved clinical responses (group 1 vs. group 2, 84.8% vs. 100%, p = 0.0316). Although the safety profile was not significantly different between the two groups, the incidence of choleliths during ceftriaxone therapy in group 1 was higher than that in group 2 (31.3% vs. 9.1%, p = 0.174). Therefore, a 2 g once daily administration of ceftriaxone appeared to be a simple regimen adequate for the treatment of inpatients with mild-to-moderate aspiration pneumonia, which might not be heavily involved by anaerobes. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Alexander Tomasz—Outstanding Contributions in the Fields of Antibiotic Resistance and Bacterial Infectious Diseases)
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9 pages, 849 KiB  
Article
Efficacy of Trimethoprim–Sulfamethoxazole in Combination with an Echinocandin as a First-Line Treatment Option for Pneumocystis Pneumonia: A Systematic Review and Meta-Analysis
by Hideo Kato, Mao Hagihara, Nobuhiro Asai, Takumi Umemura, Yuichi Shibata, Jun Hirai, Yuka Yamagishi, Takuya Iwamoto and Hiroshige Mikamo
Antibiotics 2022, 11(6), 719; https://doi.org/10.3390/antibiotics11060719 - 26 May 2022
Cited by 12 | Viewed by 3799
Abstract
Although combination therapy using trimethoprim–sulfamethoxazole (TMP–SMX) plus echinocandins has been reported to reduce the mortality of patients with pneumocystis pneumonia (PCP), it remains unclear whether it is more effective than TMP–SMX monotherapy, the current first-line treatment for this disease. Hence, we performed a [...] Read more.
Although combination therapy using trimethoprim–sulfamethoxazole (TMP–SMX) plus echinocandins has been reported to reduce the mortality of patients with pneumocystis pneumonia (PCP), it remains unclear whether it is more effective than TMP–SMX monotherapy, the current first-line treatment for this disease. Hence, we performed a systematic review and meta-analysis to compare the efficacies of these treatment options for PCP. The Scopus, EMBASE, PubMed, CINAHL, and Ichushi databases were searched for studies (up to January 2022) reporting the mortality and positive response rates (fewer clinical symptoms, improved partial pressure of arterial oxygen, and resolution of pneumonitis on chest imaging) of PCP patients receiving monotherapy or combination therapy. Four studies met the inclusion criteria. All four presented mortality data and one had positive response rates. Compared with the monotherapy, the combination therapy resulted in significantly lower mortality and higher positive response rates (mortality: odds ratio (OR) 2.20, 95% confidence interval (CI) 1.46–3.31; positive response rate: OR 2.13, 95%CI 1.41–3.23), suggesting it to be an effective and promising first-line therapy for PCP. However, further safety evaluations are needed to establish this as a fact. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Alexander Tomasz—Outstanding Contributions in the Fields of Antibiotic Resistance and Bacterial Infectious Diseases)
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13 pages, 1483 KiB  
Article
Impacts of NaHCO3 on β-Lactam Binding to PBP2a Protein Variants Associated with the NaHCO3-Responsive versus NaHCO3-Non-Responsive Phenotypes
by Selvi C. Ersoy, Liana C. Chan, Michael R. Yeaman, Henry F. Chambers, Richard A. Proctor, Kevin C. Ludwig, Tanja Schneider, Adhar C. Manna, Ambrose Cheung and Arnold S. Bayer
Antibiotics 2022, 11(4), 462; https://doi.org/10.3390/antibiotics11040462 - 30 Mar 2022
Cited by 5 | Viewed by 2323
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) regulates resistance to β-lactams via preferential production of an alternative penicillin-binding protein (PBP), PBP2a. PBP2a binds many β-lactam antibiotics with less affinity than PBPs which are predominant in methicillin-susceptible (MSSA) strains. A novel, rather frequent in vitro phenotype was [...] Read more.
Methicillin-resistant Staphylococcus aureus (MRSA) regulates resistance to β-lactams via preferential production of an alternative penicillin-binding protein (PBP), PBP2a. PBP2a binds many β-lactam antibiotics with less affinity than PBPs which are predominant in methicillin-susceptible (MSSA) strains. A novel, rather frequent in vitro phenotype was recently identified among clinical MRSA bloodstream isolates, termed “NaHCO3-responsiveness”. This phenotype features β-lactam susceptibility of certain MRSA strains only in the presence of NaHCO3. Two distinct PBP2a variants, 246G and 246E, have been linked to the NaHCO3-responsive and NaHCO3-non-responsive MRSA phenotypes, respectively. To determine the mechanistic impact of PBP2a variants on β-lactam susceptibility, binding profiles of a fluorescent penicillin probe (Bocillin-FL) to each purified PBP2a variant were assessed and compared to whole-cell binding profiles characterized by flow cytometry in the presence vs. absence of NaHCO3. These investigations revealed that NaHCO3 differentially influenced the binding of the fluorescent penicillin, Bocillin-FL, to the PBP2a variants, with binding intensity and rate of binding significantly enhanced in the 246G compared to the 246E variant. Of note, the NaHCO3-β-lactam (oxacillin)-responsive JE2 strain, which natively harbors the 246G variant, had enhanced Bocillin-FL whole-cell binding following exposure to NaHCO3. This NaHCO3-mediated increase in whole-cell Bocillin-FL binding was not observed in the NaHCO3-non-responsive parental strain, COL, which contains the 246E PBP2a variant. Surprisingly, genetic swaps of the mecA coding sites between JE2 and COL did not alter the NaHCO3-enhanced binding seen in JE2 vs. COL. These data suggest that the non-coding regions of mecA may be involved in NaHCO3-responsiveness. This investigation also provides strong evidence that the NaHCO3-responsive phenotype in MRSA may involve NaHCO3-mediated increases in both initial cell surface β-lactam binding, as well as ultimate PBP2a binding of β-lactams. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Alexander Tomasz—Outstanding Contributions in the Fields of Antibiotic Resistance and Bacterial Infectious Diseases)
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13 pages, 1950 KiB  
Article
Resistome Diversity and Dissemination of WHO Priority Antibiotic Resistant Pathogens in Lebanese Estuaries
by Wadad Hobeika, Margaux Gaschet, Marie-Cécile Ploy, Elena Buelow, Dolla Karam Sarkis and Christophe Dagot
Antibiotics 2022, 11(3), 306; https://doi.org/10.3390/antibiotics11030306 - 24 Feb 2022
Cited by 3 | Viewed by 2414
Abstract
Anthropogenic pressure is known to be a key driver of antimicrobial resistance (AMR) dissemination in the environment. Especially in lower income countries, with poor infrastructure, the level of AMR dissemination is high. Therefore, we assessed the levels and diversity of antibiotic-resistant bacteria (ARB) [...] Read more.
Anthropogenic pressure is known to be a key driver of antimicrobial resistance (AMR) dissemination in the environment. Especially in lower income countries, with poor infrastructure, the level of AMR dissemination is high. Therefore, we assessed the levels and diversity of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in Lebanese rivers at estuaries’ sites (n = 72) of the Mediterranean Sea in spring 2017 and winter 2018. Methods: A combined approach using culture techniques and high throughput qPCR were applied to identify ARB and ARGs in rivers along the Lebanese coast. Results: Multidrug-resistant Gram-negative (Enterobacterales and Pseudomonas spp.) and Gram-positive bacterial pathogens were isolated. Levels of ARGs were highest in the winter campaign and areas with high anthropogenic activities and population growth with an influx of refugees. Conclusion: Qualitative analysis of ARB and the analysis of the Lebanese estuaries’ resistome revealed critical levels of contamination with pathogenic bacteria and provided significant information about the spread of ARGs in anthropogenically impacted estuaries. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Alexander Tomasz—Outstanding Contributions in the Fields of Antibiotic Resistance and Bacterial Infectious Diseases)
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13 pages, 2820 KiB  
Article
Impact of the Stringent Stress Response on the Expression of Methicillin Resistance in Staphylococcaceae Strains Carrying mecA, mecA1 and mecC
by Catarina Milheiriço, Alexander Tomasz and Hermínia de Lencastre
Antibiotics 2022, 11(2), 255; https://doi.org/10.3390/antibiotics11020255 - 16 Feb 2022
Cited by 4 | Viewed by 2166
Abstract
The acquisition of the resistance determinant mecA by Staphylococcus aureus is of major clinical importance, since it confers a resistant phenotype to virtually the entire large family of structurally diverse β-lactam antibiotics. While the common resistance determinant mecA is essential, the optimal expression [...] Read more.
The acquisition of the resistance determinant mecA by Staphylococcus aureus is of major clinical importance, since it confers a resistant phenotype to virtually the entire large family of structurally diverse β-lactam antibiotics. While the common resistance determinant mecA is essential, the optimal expression of the resistance phenotype also requires additional factors. Previous studies showed that the great majority of clinical isolates of methicillin-resistant S. aureus (MRSA) have a heterogeneous resistant phenotype, and we observed that strains carrying methicillin genetic determinants other than mecA also produce similar heterogeneous phenotypes. All these strains were able to express high and homogeneous levels of oxacillin resistance when sub-inhibitory concentrations of mupirocin, an effector of the stringent stress response, were added to growth media. Our studies show that the gene gmk, involved in guanine metabolism, was one of the first genes to exhibit mutations in homoresistant (H*R) derivatives obtained through serial passages (with increasing concentrations of oxacillin) of the prototype mecC-carrying MRSA strain LGA251. All these observations led us to propose that a common molecular mechanism for the establishment of high and homogeneous oxacillin resistance must be present among isolates carrying different methicillin resistance determinants. In this work, we tested this hypothesis using whole-genome sequencing (WGS) to compare isogenic populations differing only in their degrees of oxacillin resistance and carrying various methicillin genetic determinants Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Alexander Tomasz—Outstanding Contributions in the Fields of Antibiotic Resistance and Bacterial Infectious Diseases)
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16 pages, 1602 KiB  
Article
FtsH Sensitizes Methicillin-Resistant Staphylococcus aureus to β-Lactam Antibiotics by Degrading YpfP, a Lipoteichoic Acid Synthesis Enzyme
by Won-Sik Yeo, Bohyun Jeong, Nimat Ullah, Majid Ali Shah, Amjad Ali, Kyeong Kyu Kim and Taeok Bae
Antibiotics 2021, 10(10), 1198; https://doi.org/10.3390/antibiotics10101198 - 1 Oct 2021
Cited by 8 | Viewed by 2736
Abstract
In the Gram-positive pathogen Staphylococcus aureus, FtsH, a membrane-bound metalloprotease, plays a critical role in bacterial virulence and stress resistance. This protease is also known to sensitize methicillin-resistant Staphylococcus aureus (MRSA) to β-lactam antibiotics; however, the molecular mechanism is not known. Here, [...] Read more.
In the Gram-positive pathogen Staphylococcus aureus, FtsH, a membrane-bound metalloprotease, plays a critical role in bacterial virulence and stress resistance. This protease is also known to sensitize methicillin-resistant Staphylococcus aureus (MRSA) to β-lactam antibiotics; however, the molecular mechanism is not known. Here, by the analysis of FtsH substrate mutants, we found that FtsH sensitizes MRSA specifically to β-lactams by degrading YpfP, the enzyme synthesizing the anchor molecule for lipoteichoic acid (LTA). Both the overexpression of FtsH and the disruption of ypfP-sensitized MRSA to β-lactams were observed. The knockout mutation in ftsH and ypfP increased the thickness of the cell wall. The β-lactam sensitization coincided with the production of aberrantly large LTA molecules. The combination of three mutations in the rpoC, vraB, and SAUSA300_2133 genes blocked the β-lactam-sensitizing effect of FtsH. Murine infection with the ypfP mutant could be treated by oxacillin, a β-lactam antibiotic ineffective against MRSA; however, the effective concentration of oxacillin differed depending on the S. aureus strain. Our study demonstrated that the β-lactam sensitizing effect of FtsH is due to its digestion of YpfP. It also suggests that the larger LTA molecules are responsible for the β-lactam sensitization phenotype, and YpfP is a viable target for developing novel anti-MRSA drugs. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Alexander Tomasz—Outstanding Contributions in the Fields of Antibiotic Resistance and Bacterial Infectious Diseases)
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20 pages, 5038 KiB  
Article
Comparative Effectiveness Study of Home-Based Interventions to Prevent CA-MRSA Infection Recurrence
by Jonathan N. Tobin, Suzanne Hower, Brianna M. D’Orazio, María Pardos de la Gándara, Teresa H. Evering, Chamanara Khalida, Jessica Ramachandran, Leidy Johana González, Rhonda G. Kost, Kimberly S. Vasquez, Hermínia de Lencastre, Alexander Tomasz, Barry S. Coller and Roger Vaughan
Antibiotics 2021, 10(9), 1105; https://doi.org/10.3390/antibiotics10091105 - 13 Sep 2021
Cited by 3 | Viewed by 3003
Abstract
Recurrent skin and soft tissue infections (SSTI) caused by Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA) or Methicillin-Sensitive Staphylococcus aureus (CA-MSSA) present treatment challenges. This community-based trial examined the effectiveness of an evidence-based intervention (CDC Guidelines, topical decolonization, surface decontamination) to reduce SSTI recurrence, mitigate [...] Read more.
Recurrent skin and soft tissue infections (SSTI) caused by Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA) or Methicillin-Sensitive Staphylococcus aureus (CA-MSSA) present treatment challenges. This community-based trial examined the effectiveness of an evidence-based intervention (CDC Guidelines, topical decolonization, surface decontamination) to reduce SSTI recurrence, mitigate household contamination/transmission, and improve patient-reported outcomes. Participants (n = 186) were individuals with confirmed MRSA(+)/MSSA(+) SSTIs and their household members. During home visits; Community Health Workers/Promotoras provided hygiene instructions; a five-day supply of nasal mupirocin; chlorhexidine for body cleansing; and household disinfecting wipes (Experimental; EXP) or Usual Care Control (UC CON) pamphlets. Primary outcome was six-month SSTI recurrence from electronic health records (EHR). Home visits (months 0; 3) and telephone assessments (months 0; 1; 6) collected self-report data. Index patients and participating household members provided surveillance culture swabs. Secondary outcomes included household surface contamination; household member colonization and transmission; quality of life; and satisfaction with care. There were no significant differences in SSTI recurrence between EXP and UC in the intent-to-treat cohort (n = 186) or the enrolled cohort (n = 119). EXP participants showed reduced but non-significant colonization rates. EXP and UC did not differ in household member transmission, contaminated surfaces, or patient-reported outcomes. This intervention did not reduce clinician-reported MRSA/MSSA SSTI recurrence. Taken together with other recent studies that employed more intensive decolonization protocols, it is possible that a promotora-delivered intervention instructing treatment for a longer or repetitive duration may be effective and should be examined by future studies. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Alexander Tomasz—Outstanding Contributions in the Fields of Antibiotic Resistance and Bacterial Infectious Diseases)
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Review

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16 pages, 2075 KiB  
Review
Lung-Directed Bacteriotherapy in Cystic Fibrosis: Could It Be an Option?
by Giovanna Batoni, Giuseppantonio Maisetta, Esingül Kaya and Semih Esin
Antibiotics 2022, 11(3), 326; https://doi.org/10.3390/antibiotics11030326 - 28 Feb 2022
Cited by 9 | Viewed by 3339
Abstract
Due to the alarming spread of bacterial resistance to conventional drugs, the sole use of antibiotics to fight lung infections in cystic fibrosis (CF) is not resolutive, and novel strategies to replace or complement the use of antibiotics are highly desirable. Among these [...] Read more.
Due to the alarming spread of bacterial resistance to conventional drugs, the sole use of antibiotics to fight lung infections in cystic fibrosis (CF) is not resolutive, and novel strategies to replace or complement the use of antibiotics are highly desirable. Among these strategies, the use of probiotics is emerging as a particularly attractive approach. Probiotic administration via the oral route has demonstrated an ability to improve lung function and to reduce infection and exacerbation rates in CF patients through mechanisms mainly attributable to the gut–lung axis. Nevertheless, some studies reported no beneficial effect of probiotic intake suggesting that there is margin for improvement of such innovative intervention in CF. The present review aims to address the rationale behind probiotic use in CF and discuss the hypothesis that nasal/aerosol administration of appropriate probiotic strains may help to exert a direct beneficial effect on the respiratory tract, increasing the effectiveness of probiotic interventions in CF patients. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Alexander Tomasz—Outstanding Contributions in the Fields of Antibiotic Resistance and Bacterial Infectious Diseases)
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Other

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8 pages, 842 KiB  
Brief Report
Penetration through Outer Membrane and Efflux Potential in Pseudomonas aeruginosa of Bulgecin A as an Adjuvant to β-Lactam Antibiotics
by Choon Kim, Shusuke Tomoshige, Mijoon Lee, Helen I. Zgurskaya and Shahriar Mobashery
Antibiotics 2023, 12(2), 358; https://doi.org/10.3390/antibiotics12020358 - 9 Feb 2023
Cited by 1 | Viewed by 1698
Abstract
The treatment of infections by Gram-negative bacteria remains a difficult clinical challenge. In the light of the dearth of discovery of novel antibiotics, one strategy that is being explored is the use of adjuvants to enhance antibacterial activities of existing antibiotics. One such [...] Read more.
The treatment of infections by Gram-negative bacteria remains a difficult clinical challenge. In the light of the dearth of discovery of novel antibiotics, one strategy that is being explored is the use of adjuvants to enhance antibacterial activities of existing antibiotics. One such adjuvant is bulgecin A, which allows for the lowering of minimal-inhibitory concentrations for β-lactam antibiotics. We have shown that bulgecin A inhibits three of the pseudomonal lytic transglycosylases in its mode of action, yet high concentrations are needed for potentiation activity. Herein, we document that bulgecin A is not a substrate for pseudomonal efflux pumps, whose functions could have been a culprit in the need for high concentrations. We present evidence that the penetration barrier into the periplasm is at the root of the need for high concentrations of bulgecin A in its potentiation of β-lactam antibiotics. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Alexander Tomasz—Outstanding Contributions in the Fields of Antibiotic Resistance and Bacterial Infectious Diseases)
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21 pages, 1494 KiB  
Systematic Review
Wild Animals Are Reservoirs and Sentinels of Staphylococcus aureus and MRSA Clones: A Problem with “One Health” Concern
by Idris Nasir Abdullahi, Rosa Fernández-Fernández, Guillermo Juárez-Fernández, Sandra Martínez-Álvarez, Paula Eguizábal, Myriam Zarazaga, Carmen Lozano and Carmen Torres
Antibiotics 2021, 10(12), 1556; https://doi.org/10.3390/antibiotics10121556 - 20 Dec 2021
Cited by 38 | Viewed by 6509
Abstract
Background: The availability of comprehensive data on the ecology and molecular epidemiology of Staphylococcus aureus/MRSA in wild animals is necessary to understand their relevance in the “One Health” domain. Objective: In this study, we determined the pooled prevalence of nasal, tracheal and/or [...] Read more.
Background: The availability of comprehensive data on the ecology and molecular epidemiology of Staphylococcus aureus/MRSA in wild animals is necessary to understand their relevance in the “One Health” domain. Objective: In this study, we determined the pooled prevalence of nasal, tracheal and/or oral (NTO) Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA) carriage in wild animals, with a special focus on mecA and mecC genes as well as the frequency of MRSA and methicillin susceptible S. aureus (MSSA) of the lineages CC398 and CC130 in wild animals. Methodology: This systematic review was executed on cross-sectional studies that reported S. aureus and MRSA in the NTO cavities of wild animals distributed in four groups: non-human primates (NHP), wild mammals (WM, excluding rodents and NHP), wild birds (WB) and wild rodents (WR). Appropriate and eligible articles published (in English) between 1 January 2011 to 30 August 2021 were searched for from PubMed, Scopus, Google Scholar, SciElo and Web of Science. Results: Of the 33 eligible and analysed studies, the pooled prevalence of NTO S. aureus and MRSA carriage was 18.5% (range: 0–100%) and 2.1% (range: 0.0–63.9%), respectively. The pooled prevalence of S. aureus/MRSA in WM, NHP, WB and WR groups was 15.8/1.6, 32.9/2.0, 10.3/3.4 and 24.2/3.4%, respectively. The prevalence of mecC-MRSA among WM/NHP/WB/WR was 1.64/0.0/2.1/0.59%, respectively, representing 89.9/0.0/59.1/25.0% of total MRSA detected in these groups of animals.The MRSA-CC398 and MRSA-CC130 lineages were most prevalent in wild birds (0.64 and 2.07%, respectively); none of these lineages were reported in NHP studies. The MRSA-CC398 (mainly of spa-type t011, 53%), MRSA-CC130 (mainly of spa types t843 and t1535, 73%), MSSA-CC398 (spa-types t571, t1451, t6606 and t034) and MSSA-CC130 (spa types t843, t1535, t3625 and t3256) lineages were mostly reported. Conclusion: Although the global prevalence of MRSA is low in wild animals, mecC-mediated resistance was particularly prevalent among MRSA isolates, especially among WM and WB. Considering the genetic diversity of MRSA in wild animals, they need to be monitored for effective control of the spread of antimicrobial resistance. Full article
(This article belongs to the Special Issue A Themed Issue in Honor of Professor Alexander Tomasz—Outstanding Contributions in the Fields of Antibiotic Resistance and Bacterial Infectious Diseases)
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