Catestatin selects for the colonization of antimicrobial-resistant gut bacterial communities

2021 ◽  
Author(s):  
Pamela González-Dávila ◽  
Markus Schwalbe ◽  
Arpit Danewalia ◽  
Boushra Dalile ◽  
Kristin Verbeke ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Resistance ◽  
Defense Mechanism ◽  
Short Chain Fatty Acids ◽  
Resistance Mechanisms ◽  
Coding Region ◽  
Disease States ◽  
Innermost Layer ◽  
Continuous Interaction ◽  
Secreted Peptides

The gut microbiota is in continuous interaction with the innermost layer of the gut, namely the epithelium. Among the various functions of the gut epithelium, is to keep the microbes at bay to avoid overstimulation of the underlying mucosa immune cells. To do so, the gut epithelia secrete a variety of antimicrobial peptides, such as catestatin (CST). As a defense mechanism, gut microbes have evolved antimicrobial resistance mechanisms to counteract the killing effect of the secreted peptides. To this end, we treated wild-type mice and mice with a knockout in the CST coding region of the chromogranin-A gene (CST-KO) with CST for 15 consecutive days. CST treatment was associated with a shift in the diversity and composition of the microbiota in the CST-KO mice. This effect was less prominent in WT mice. Levels of the microbiota-produced short-chain fatty acids, in particular, butyrate and acetate were significantly increased in CST-treated CST-KO mice but not the WT group. Remarkably, both CST-treated CST-KO and WT mice showed a significant increase in microbiota-harboring phosphoethanolamine transferase-encoding genes, which facilitate their antimicrobial resistance. Finally, we show that CST was degraded by Escherichia coli via an omptin-protease and that the abundance of this gene was significantly higher in metagenomic datasets collected from patients with Crohn's disease but not with ulcerative colitis. Overall, this study illustrates how the endogenous antimicrobial peptide, CST, shapes the microbiota composition in the gut and primes further research to uncover the role of bacterial resistance to CST in disease states such as inflammatory bowel disease.

Antibiotic Cycling and Marketing Into the 21st Century: A Perspective From the Pharmaceutical Industry

2000 ◽  
Vol 21 (S1) ◽  
pp. S32-S35 ◽  
Author(s):  
Bruce S. Lavin
Keyword(s):  
Antimicrobial Resistance ◽  
Pharmaceutical Industry ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Resistance Mechanisms ◽  
Medical Community ◽  
Resistant Bacteria ◽  
Environmental Pressures ◽  
Development Of Resistance ◽  
Antibiotic Cycling

AbstractBefore the development of the first antimicrobial agents, bacteria already had demonstrated an ability to adapt to stress in the environment, resulting in the development of resistance that often makes the prevailing antibiotic treatment ineffective. The response to antimicrobial resistance in the medical community has been to use new or alternative antibiotics not previously used against the resistant bacteria. The pharmaceutical industry has responded to the resistance problem by producing newer antibiotics, either as modifications of currently existing compounds or as combinations of compounds that may inhibit or bypass the bacterial resistance mechanisms. The development of new antibiotics is a lengthy and costly process. To be successful, the pharmaceutical industry must anticipate the changing needs of the medical community, as well as the dynamic process of antimicrobial resistance. The marketing of new antimicrobial agents must be adaptable to the potential environmental pressures that induce bacterial resistance in order to ensure the longevity of the agents.

scholarly journals Bacterial Resistance to Antimicrobial Agents

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 593
Author(s):  
Manuel F. Varela ◽  
Jerusha Stephen ◽  
Manjusha Lekshmi ◽  
Manisha Ojha ◽  
Nicholas Wenzel ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Drug Targets ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Health Sector ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Cellular Mechanisms ◽  
Causative Agents

Bacterial pathogens as causative agents of infection constitute an alarming concern in the public health sector. In particular, bacteria with resistance to multiple antimicrobial agents can confound chemotherapeutic efficacy towards infectious diseases. Multidrug-resistant bacteria harbor various molecular and cellular mechanisms for antimicrobial resistance. These antimicrobial resistance mechanisms include active antimicrobial efflux, reduced drug entry into cells of pathogens, enzymatic metabolism of antimicrobial agents to inactive products, biofilm formation, altered drug targets, and protection of antimicrobial targets. These microbial systems represent suitable focuses for investigation to establish the means for their circumvention and to reestablish therapeutic effectiveness. This review briefly summarizes the various antimicrobial resistance mechanisms that are harbored within infectious bacteria.

Emerging Antimicrobial Resistance Among Methicillin Resistant Staphylococcus Aureus (MRSA) in a Tertiary Care Centre in North India

JMS SKIMS ◽  
2020 ◽  
Vol 23 (1) ◽  
pp. 48-49
Author(s):  
Javaid Ahmad Bhat ◽  
Shariq Rashid Masoodi
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Resistance ◽  
Tertiary Care ◽  
Resistance Mechanisms ◽  
North India ◽  
Global Public Health ◽  
Care Centre ◽  
Tertiary Care Centre ◽  
Effective Prevention ◽  
Mupirocin Resistance

Apropos to the article by Dr Bali, titled “Mupirocin resistance in clinical isolates of methicillin-sensitive and resistant Staphylococcus aureus in a tertiary care centre of North India” (1), the authors have raised important issue of emerging antimicrobial resistance (AMR). Antimicrobial resistance is an increasingly serious threat to global public health that requires action across all government sectors and society. As per WHO, AMR lurks the effective prevention and management of an ever-increasing spectrum of infections caused by bacteria, parasites, fungi and viruses. Novel resistance mechanisms are emerging and spreading globally, threatening the man’s ability to treat common infectious diseases.

Microarray Technology for the Detection of Antimicrobial Resistance Genes Present in Hospital and Community Acquired Methicillin Resistant S.aureus Strains

2017 ◽  
Vol 68 (11) ◽  
pp. 2546-2550
Author(s):  
Monica Licker ◽  
Andrei Anghel ◽  
Roxana Moldovan ◽  
Elena Hogea ◽  
Delia Muntean ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Dna Microarray ◽  
Bacterial Resistance ◽  
Meca Gene ◽  
Modern Medicine ◽  
Microarray Technology ◽  
Methicillin Resistant ◽  
Antimicrobial Sensitivity ◽  
Antimicrobial Resistance Genes ◽  
Mrsa Strains

Antimicrobial resistance (AMR) represents a real burden for the modern medicine. One of the most frecvently isolated hospital acquired (HA) pathogens wordlwide, is Methicillin resistant Staphylococcus aureus (MRSA). Recently not only HA, but also community-acquired MRSA (CA-MRSA) infections have been reported. A prospective study was performed between February 2009 and October 2010, with the aim to investigate bacterial resistance of CA-MRSA and HA-MRSA. DNA microarray technology has been used for the detection of 4 AMR genes for the studied MRSA strains. A number of 218 HA- S.aureus strains have been isolated, from which 89 (40. 82%) were MRSA. In the community, 1.553 S.aureus strains were isolated, out of which, 356 (22. 92%) were MRSA. From these, a number of 17 HA and 12 CA �MRSA strains have been analyzed by DNA microarray technology. From 100% phenotypically described HA- MRSA, we identified mecA gene in 10 strains (58. 83%). Other 6 strains (35. 29%) have been erm(A) positive and 4 (23. 53%) - tet(O) positive. 83. 33% (10 strains) from the CA strains had mecA gene, only one (8. 33%) was erm(A) positive and 4 (33. 33%) were erm(C) positive. DNA microarray is a method allowing the concomitant scan of multiple genes and can be done within a few hours. That type of rapid and reliable methods for antimicrobial sensitivity tests are important to start an appropriate therapy.

scholarly journals Clinical and microbiological characteristics of nosocomial, healthcare-associated, and community-acquired Klebsiella pneumoniae infections in Guangzhou, China

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Tingting Le ◽  
Ling Wang ◽  
Chaoying Zeng ◽  
Leiwen Fu ◽  
Zhihua Liu ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
Bacterial Resistance ◽  
Empirical Therapy ◽  
Clonal Diversity ◽  
Extended Spectrum Beta Lactamase ◽  
Microbiological Characteristics ◽  
Carbapenemase Gene ◽  
Cross Transmission ◽  
Healthcare Associated

Abstract Background Klebsiella pneumoniae (K. pneumoniae) is a common pathogen associated with hospital and community-onset infections. This study aimed to compare the clinical and microbiological characteristics of nosocomial, healthcare-associated (HCA), and community-acquired (CA) K. pneumoniae infections. Methods Clinical data were extracted from electronic medical records and analyzed retrospectively. Antimicrobial susceptibility and extended-spectrum beta-lactamase (ESBL) production were determined for all identified strains. Carbapenemase and ESBL genes were amplified by PCR. Genotyping of carbapenem-resistant K. pneumoniae (CRKP) and ESBL-producing strains was performed by pulsed-field gel electrophoresis (PFGE). Results Of 379 K. pneumoniae infections, 98 (25.9%) were nosocomial, 195 (51.5%) were healthcare-associated, and 86 (22.6%) were community-acquired. Hematological malignancy (OR = 4.467), and hypertension (OR = 2.08) and cerebral vascular disease (OR = 2.486) were associated with nosocomial and HCA infections respectively, when compared to CA infections. Overall, the incidence of antimicrobial resistance for the majority of agents tested was similar between nosocomial and HCA infections (P > 0.05) and both groups had a higher incidence than CA infections (P < 0.05). Moreover, 95.1% (78/82) of CRKP strains were isolated from the nosocomial and HCA groups. The blaKPC was the most prevalent carbapenemase gene among CRKP strains (80.5%, 66/82). ESBL-producing strains were prevalent among nosocomial (40.8%), HCA (35.9%) and CA groups (24.4%). The blaCTX-M-9-group and blaCTX-M-1-group genes were predominant in nosocomial (65.0%) and CA strains (66.7%), respectively. PFGE results showed ESBL-producing and CRKP strains were genetically diverse. Identical PFGE profiles were observed among HCA and nosocomial strains. Conclusions Nosocomial and HCA K. pneumoniae infections presented similar clinical features and antimicrobial resistance, and both two types of infections were different to CA infections. CRKP and ESBL-producing strains were disseminated mainly in HCA and nosocomial groups, and showed a clonal diversity. The cross transmission of CRKP was existed among HCA and nosocomial patients. This finding suggests that similar empirical therapy should be considered for patients with nosocomial and HCA K. pneumoniae infections and bacterial resistance surveillance of these infections is necessary.

scholarly journals Antimicrobials and Food-Related Stresses as Selective Factors for Antibiotic Resistance along the Farm to Fork Continuum

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 671
Author(s):  
Federica Giacometti ◽  
Hesamaddin Shirzad-Aski ◽  
Susana Ferreira
Keyword(s):  
Antibiotic Resistance ◽  
Food Safety ◽  
Antimicrobial Resistance ◽  
Food Processing ◽  
Resistance Mechanisms ◽  
Human Environment ◽  
Real Risk ◽  
Cross Adaptation ◽  
Novel Approaches

Antimicrobial resistance (AMR) is a global problem and there has been growing concern associated with its widespread along the animal–human–environment interface. The farm-to-fork continuum was highlighted as a possible reservoir of AMR, and a hotspot for the emergence and spread of AMR. However, the extent of the role of non-antibiotic antimicrobials and other food-related stresses as selective factors is still in need of clarification. This review addresses the use of non-antibiotic stressors, such as antimicrobials, food-processing treatments, or even novel approaches to ensure food safety, as potential drivers for resistance to clinically relevant antibiotics. The co-selection and cross-adaptation events are covered, which may induce a decreased susceptibility of foodborne bacteria to antibiotics. Although the available studies address the complexity involved in these phenomena, further studies are needed to help better understand the real risk of using food-chain-related stressors, and possibly to allow the establishment of early warnings of potential resistance mechanisms.

scholarly journals Impact of Ceftiofur Administration in Steers on the Prevalence and Antimicrobial Resistance of Campylobacter spp.

2021 ◽  
Vol 9 (2) ◽  
pp. 318
Author(s):  
Sicun Fan ◽  
Derek Foster ◽  
William G. Miller ◽  
Jason Osborne ◽  
Sophia Kathariou
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Resistance ◽  
Active Drug ◽  
Free Acid ◽  
Structural Similarity ◽  
Drug Concentrations ◽  
Pre Treatment ◽  
Ceftiofur Hydrochloride ◽  
Campylobacter Spp

Bacterial resistance to ceftiofur raises health concerns due to ceftiofur’s extensive veterinary usage and structural similarity with the human antibiotic ceftriaxone. Ceftiofur crystalline-free acid (CCFA) and ceftiofur hydrochloride (CHCL) are ceftiofur types used therapeutically in cattle, but their potential impacts on Campylobacter prevalence and antimicrobial resistance remain unclear. In this study two groups of steers were each treated with CCFA or CHCL. In vivo active drug concentrations were measured and fecal samples were analyzed for Campylobacter for up to 42 days post-treatment. Following administration, the colonic concentration of ceftiofur initially increased then dropped to pre-treatment levels by day 8. The estimated prevalence of Campylobacter spp. was significantly (p = 0.0009) higher during the first week after CCFA treatment than after CHCL treatment (81.3% vs. 45.2%). Campylobacter jejuni predominated overall, with other Campylobacter spp. mainly identified in the first week after CCFA treatment. No treatment impacts were noted on ceftiofur minimum inhibitory concentration (MIC) for C. jejuni (10–20 μg/mL). More C. jejuni genotypes were detected in CCFA-treated than CHCL-treated steers. These findings suggest that ceftiofur did not significantly impact Campylobacter prevalence or ceftiofur MIC. However, CHCL may be preferable due to the lower likelihood of temporary increases in Campylobacter prevalence.

scholarly journals Resistance and Adaptation of Bacteria to Non-Antibiotic Antibacterial Agents: Physical Stressors, Nanoparticles, and Bacteriophages

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 435
Author(s):  
Sada Raza ◽  
Kinga Matuła ◽  
Sylwia Karoń ◽  
Jan Paczesny
Keyword(s):  
Antimicrobial Resistance ◽  
Antibacterial Agents ◽  
Uv Light ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Physical Factors ◽  
Defense Systems ◽  
Drug Resistant Bacteria

Antimicrobial resistance is a significant threat to human health worldwide, forcing scientists to explore non-traditional antibacterial agents to support rapid interventions and combat the emergence and spread of drug resistant bacteria. Many new antibiotic-free approaches are being developed while the old ones are being revised, resulting in creating unique solutions that arise at the interface of physics, nanotechnology, and microbiology. Specifically, physical factors (e.g., pressure, temperature, UV light) are increasingly used for industrial sterilization. Nanoparticles (unmodified or in combination with toxic compounds) are also applied to circumvent in vivo drug resistance mechanisms in bacteria. Recently, bacteriophage-based treatments are also gaining momentum due to their high bactericidal activity and specificity. Although the number of novel approaches for tackling the antimicrobial resistance crisis is snowballing, it is still unclear if any proposed solutions would provide a long-term remedy. This review aims to provide a detailed overview of how bacteria acquire resistance against these non-antibiotic factors. We also discuss innate bacterial defense systems and how bacteriophages have evolved to tackle them.

Antimicrobial resistance mechanisms, MLST and NG-STAR sequence types of diverse Neisseria gonorrhoeae isolates in KwaZulu-Natal, South Africa

2021 ◽  
Author(s):  
Nireshni Mitchev ◽  
Ravesh Singh ◽  
Mushal Allam ◽  
Stanford Kwenda ◽  
Arshad Ismail ◽  
...  
Keyword(s):  
South Africa ◽  
Antimicrobial Resistance ◽  
Neisseria Gonorrhoeae ◽  
Point Mutations ◽  
Resistance Mechanisms ◽  
Public Healthcare ◽  
Multiple Sequence ◽  
Genotypic Analysis ◽  
Kwazulu Natal ◽  
Sequence Types

Objective: Antimicrobial resistance (AMR) is a major challenge to managing infectious diseases. Africa has the highest incidence of gonorrhoea but there is a lack of comprehensive data from sparse surveillance programs. This study investigated the molecular epidemiology and AMR profiles of Neisseria gonorrhoeae isolates in KwaZulu-Natal province (KZN), South Africa. Methods: Repository isolates, from patients attending public healthcare clinics for STI care, were used for phenotypic and genotypic analysis. Etest® was performed to determine antimicrobial susceptibility. Whole-genome sequencing (WGS) was used to determine epidemiology and to predict susceptibility by detecting resistance-associated genes and mutations. Results: Among the 61 isolates, multiple sequence types were identified. Six isolates were novel as determined by multilocus sequence typing. N.gonorrhoeae Sequence Typing for Antimicrobial Resistance (NG-STAR) determined 48 sequence types, of which 35 isolates had novel antimicrobial profiles. Two novel penA alleles and eight novel mtrR alleles were identified. Point mutations were detected in gyrA , parC , mtrR , penA , ponA and porB1 . This study revealed a high prevalence of AMR (penicillin 67%, tetracycline 89% and ciprofloxacin 52%). However, spectinomycin, cefixime, ceftriaxone and azithromycin remained 100% effective. Conclusion: This study is one of the first to comprehensively describe the epidemiology and AMR of N. gonorrhoeae in KZN, South Africa and Africa, using WGS. KZN has a wide strain diversity and most of these sequence types have been detected in multiple countries, however more than half of our isolates have novel antimicrobial profiles. Continued surveillance is crucial to monitor the emergence of resistance to cefixime, ceftriaxone and azithromycin.

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