scholarly journals A pentagonal hydrogen-bond network facilitates an exceptional preference for asparagine in the S2 subsite of Stenotrophomonas maltophilia dipeptidyl peptidase 7

2021 ◽  
Author(s):  
Akihiro Nakamura ◽  
Yoshiyuki Suzuki ◽  
Yasumitsu Sakamoto ◽  
Saori Roppongi ◽  
Chisato Kushibiki ◽  
...  
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Molecular Mechanisms ◽  
Substrate Preference ◽  
Resistant Bacteria ◽  
Drug Resistant Bacteria ◽  
The Family ◽  
Hydrophobic Amino Acids ◽  
Dipeptidyl Peptidases ◽  
Biochemical Analyses ◽  
S2 Subsite

Abstract The emergence of drug-resistant bacteria has become a major problem worldwide. Bacterial dipeptidyl peptidases 7 and 11 (DPP7s and DPP11s), belonging to the family-S46 peptidases, are important enzymes for bacterial growth and are not present in mammals. Therefore, specific inhibitors for these peptidases are promising as potential antibiotics. While the molecular mechanisms underlining strict substrate specificity at the S1 subsite of S46 peptidases have been well studied, those of relatively broad substrate preference at the S2 subsite of these peptidases are unknown. In this study, we performed structural and biochemical analyses on DPP7 from Stenotrophomonas maltophilia (SmDPP7). SmDPP7 showed substrate preference for hydrophobic amino acids at the S2 subsite in general, but as an exception, also for asparagine, a hydrophilic amino acid. Structural analyses of SmDPP7 revealed that this exceptional preference to asparagine is caused by a hydrogen bonding network at the bottom of the S2 subsite. The residues in the S2 subsite are well conserved among S46 peptidases as compared with those in the S1 subsite. We expect that our findings will contribute toward the development of a universal inhibitor of S46 peptidases. (184 words / 200 words)

scholarly journals Structural basis for an exceptionally strong preference for asparagine residue at the S2 subsite of Stenotrophomonas maltophilia dipeptidyl peptidase 7

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Akihiro Nakamura ◽  
Yoshiyuki Suzuki ◽  
Yasumitsu Sakamoto ◽  
Saori Roppongi ◽  
Chisato Kushibiki ◽  
...  
Keyword(s):  
Stenotrophomonas Maltophilia ◽  
Molecular Mechanisms ◽  
Structural Basis ◽  
Resistant Bacteria ◽  
Drug Resistant Bacteria ◽  
The Family ◽  
Hydrophobic Amino Acids ◽  
Biochemical Analyses ◽  
Strict Specificity ◽  
S2 Subsite

AbstractThe emergence of drug-resistant bacteria has become a major problem worldwide. Bacterial dipeptidyl peptidases 7 and 11 (DPP7s and DPP11s), belonging to the family-S46 peptidases, are important enzymes for bacterial growth and are not present in mammals. Therefore, specific inhibitors for these peptidases are promising as potential antibiotics. While the molecular mechanisms underlining strict specificity at the S1 subsite of S46 peptidases have been well studied, those of relatively broad preference at the S2 subsite of these peptidases are unknown. In this study, we performed structural and biochemical analyses on DPP7 from Stenotrophomonas maltophilia (SmDPP7). SmDPP7 showed preference for the accommodation of hydrophobic amino acids at the S2 subsite in general, but as an exception, also for asparagine, a hydrophilic amino acid. Structural analyses of SmDPP7 revealed that this exceptional preference to asparagine is caused by a hydrogen bonding network at the bottom of the S2 subsite. The residues in the S2 subsite are well conserved among S46 peptidases as compared with those in the S1 subsite. We expect that our findings will contribute toward the development of a universal inhibitor of S46 peptidases.

scholarly journals Mechanism and challenges associated with adaptation and evolution of drug-resistant bacteria: an overview

2020 ◽  
pp. 1-18
Author(s):  
Shikha Kapil ◽  
Tarun Kumar ◽  
Vipasha Sharma
Keyword(s):  
Antimicrobial Resistance ◽  
Molecular Mechanisms ◽  
Antimicrobial Agents ◽  
Resistant Bacteria ◽  
Random Mutation ◽  
Protein Carriers ◽  
Drug Resistant Bacteria ◽  
Global Issue ◽  
Evolution Of Resistance ◽  
Vertical Evolution

Antimicrobial resistance is one of the leading challenges in the human healthcare segment. Advances in antimicrobial resistance studies have revealed various intrinsic, adaptive or acquired factors to be involved for pathogenicity. Antimicrobial agents are either bactericidal or bacteriostatic in action and prescribed according to the mode of action. Various factors are confined for the antimicrobial activity of these agents via biochemical, mechanical, physiological and molecular mechanisms. Microbial cell expresses a number of alternates responsible for the evolution of resistance against these agent activities involving cell surface modifications, enzyme inhibitions, modifications in efflux system, protein carriers and mutations in nucleic acids. Apart from this, the successful adaptations of such microbes have also been observed with the transfer of responsible genes through miscellaneous operations such as vertical evolution, horizontal gene transfer, co-selection, compensatory and random mutation. In addition, alterations or modifications in biochemical and physiological mechanisms at cellular levels are also responsible for antibiotic resistance. This article briefly shows the present scenario of antimicrobial resistance and the alternatives to overcome this global issue in future.

scholarly journals Current Mechanism of Bacterial Resistance to Antimicrobials

2018 ◽  
Vol 10 (01) ◽  
pp. 55-64
Author(s):  
Sonali Gangwar ◽  
Keerti Kaushik ◽  
Maya Datt Joshi
Keyword(s):  
Molecular Mechanisms ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Hospital Environment ◽  
Health Concern ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Pathogenic Variants ◽  
Drug Resistant Bacteria

Serious infectious diseases are caused by bacterial pathogens that represents a serious public health concern. Antimicrobial agents are indicated for the treatment bacterial infections.Various bacteria carries several resistance genes also called multidrug resistant (MDR). Multidrug resistant organisms have emerged not only in the hospital environment but are now often identified in community settings, suggesting the reservoirs of antibiotic resistant bacteria are present outside the hospital. Drug resistant bacteria that are selected with a single drug are also frequently multi-drug resistant against multiple structurally different drugs, thus confounding the chemotherapeutic efficacy of infectious disease caused by such pathogenic variants. The molecular mechanisms by which bacteria have common resistance to antibiotics are diverse and complex. This review highlights the mechanism of bacterial resistance to antimicrobials.

Current Mechanism of Bacterial Resistance to Antimicrobials

2018 ◽  
Vol 10 (1) ◽  
Author(s):  
Sonali Gangwar ◽  
Keerti Kaushik ◽  
Maya Datt Joshi
Keyword(s):  
Molecular Mechanisms ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Hospital Environment ◽  
Health Concern ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Pathogenic Variants ◽  
Drug Resistant Bacteria

Serious infectious diseases are caused by bacterial pathogens that represents a serious public health concern. Antimicrobial agents are indicated for the treatment bacterial infections.Various bacteria carries several resistance genes also called multidrug resistant (MDR). Multidrug resistant organisms have emerged not only in the hospital environment but are now often identified in community settings, suggesting the reservoirs of antibiotic resistant bacteria are present outside the hospital. Drug resistant bacteria that are selected with a single drug are also frequently multi-drug resistant against multiple structurally different drugs, thus confounding the chemotherapeutic efficacy of infectious disease caused by such pathogenic variants. The molecular mechanisms by which bacteria have common resistance to antibiotics are diverse and complex. This review highlights the mechanism of bacterial resistance to antimicrobials.

Novel Antibiotics from Marine Sources

2011 ◽  
Vol 4 (3) ◽  
pp. 1446-1461 ◽  
Author(s):  
E.A. Martis ◽  
G M Doshi ◽  
G V Aggarwal ◽  
P P Shanbhag
Keyword(s):  
Pharmaceutical Industry ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Drug Resistant Bacteria ◽  
Terrestrial Life ◽  
New Antibiotics ◽  
Antibiotic Compounds ◽  
New Generation ◽  
Novel Antibiotics ◽  
Untapped Resource

With the emergence of newer diseases, resistant forms of infectious diseases and multi-drug resistant bacteria, it has become essential to develop novel and more effective antibiotics. Current antibiotics are obtained from terrestrial life or made synthetically from intermediates. The ocean represents virtually untapped resource from which novel antibiotic compounds can be discovered. It is the marine world that will provide the pharmaceutical industry with the next generation of antibiotics. Marine antibiotics are antibiotics obtained from marine organisms. Scientists have reported the discovery of various antibiotics from marine bacteria (aplasmomycin, himalomycins, and pelagiomycins), sponges (Ara C, variabillin, strobilin, ircinin-1, aeroplysin, 3,5-dibromo-4-hydroxyphenylacetamide), coelenterates (asperidol and eunicin), mollusks (laurinterol and pachydictyol), tunicates (geranylhydroquinone and cystadytins), algae (cycloeudesmol, aeroplysinin-1(+), prepacifenol and tetrabromoheptanone), worms (tholepin and 3,5-dibromo-4-hydroxybezaldehyde), and actinomycetes (marinomycins C and D). This indicates that the marine environment, representing approximately half of the global diversity, is an enormous resource for new antibiotics and this source needs to be explored for the discovery of new generation antibiotics. The present article provides an overview of various antibiotics obtained from marine sources.

Re-challenging antibiotic resistance with Daniel Berman

2020 ◽  
Author(s):  
Daniel Berman
Keyword(s):  
Bacterial Infections ◽  
Point Of Care ◽  
Healthcare Setting ◽  
Rapid Diagnostic Tests ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Drug Resistant Bacteria ◽  
Global Threat ◽  
The Right ◽  
Point Of Care Tests

How can we prevent the rise of resistance to antibiotics? In this video, Daniel Berman,  Nesta Challenges, discusses the global threat of AMR and how prizes like the Longitude Prize can foster the development of rapid diagnostic tests for bacterial infections, helping to contribute towards reducing the global threat of drug resistant bacteria. Daniel outlines how accelerating the development of rapid point-of-care tests will ensure that bacterial infections are treated with the most appropriate antibiotic, at the right time and in the right healthcare setting.

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