scholarly journals Pathogen invasion-dependent tissue reservoirs and plasmid-encoded antibiotic degradation boost plasmid spread in the gut

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Erik Bakkeren ◽  
Joana Anuschka Herter ◽  
Jana Sanne Huisman ◽  
Yves Steiger ◽  
Ersin Gül ◽  
...  

Many plasmids encode antibiotic resistance genes. Through conjugation, plasmids can be rapidly disseminated. Previous work identified gut luminal donor/recipient blooms and tissue-lodged plasmid-bearing persister cells of the enteric pathogen Salmonella enterica serovar Typhimurium (S.Tm) that survive antibiotic therapy in host tissues, as factors promoting plasmid dissemination among Enterobacteriaceae. However, the buildup of tissue reservoirs and their contribution to plasmid spread await experimental demonstration. Here, we asked if re-seeding-plasmid acquisition-invasion cycles by S.Tm could serve to diversify tissue-lodged plasmid reservoirs, and thereby promote plasmid spread. Starting with intraperitoneal mouse infections, we demonstrate that S.Tm cells re-seeding the gut lumen initiate clonal expansion. Extended spectrum beta-lactamase (ESBL) plasmid-encoded gut luminal antibiotic degradation by donors can foster recipient survival under beta-lactam antibiotic treatment, enhancing transconjugant formation upon re-seeding. S.Tm transconjugants can subsequently re-enter host tissues introducing the new plasmid into the tissue-lodged reservoir. Population dynamics analyses pinpoint recipient migration into the gut lumen as rate-limiting for plasmid transfer dynamics in our model. Priority effects may be a limiting factor for reservoir formation in host tissues. Overall, our proof-of-principle data indicates that luminal antibiotic degradation and shuttling between the gut lumen and tissue-resident reservoirs can promote the accumulation and spread of plasmids within a host over time.

2021 ◽  
Author(s):  
Erik Bakkeren ◽  
Joana A Herter ◽  
Jana Sanne Huisman ◽  
Ersin Gul ◽  
Alexander Oliver Brachmann ◽  
...  

Many plasmids encode antibiotic resistance genes. Through conjugation, such plasmids can rapidly disseminate between bacterial strains. Previous work has identified gut-luminal donor/recipient blooms and tissue-lodged plasmid-bearing persister cells of the enteric pathogen Salmonella enterica serovar Typhimurium (S.Tm) that survive antibiotic-therapy in host tissues, as factors promoting plasmid dissemination among Enterobacteriaceae. However, the buildup of tissue reservoirs and their contribution to plasmid spread await experimental demonstration. Here, we asked if reseeding-acquisition-invasion cycles by S.Tm could serve to diversify tissue-lodged plasmid reservoirs, and thereby promote plasmid spread. Starting with intraperitoneal mouse infections, we demonstrate that S.Tm reseeding the gut lumen from either growing populations or persisters initiates clonal expansion. ESBL plasmid-encoded gut luminal antibiotic degradation by donors can foster recipient survival under beta-lactam antibiotic treatment, enhancing transconjugant formation upon reseeding. S.Tm transconjugants can subsequently re-enter host tissues introducing the new plasmid into the tissue-lodged reservoir. Population dynamics analyses pinpoint recipient migration into the gut lumen as rate-limiting for plasmid transfer dynamics in our model. Priority effects may limit reservoir formation in host tissues. Once transconjugant reservoirs are formed, persisters and chronically infecting transconjugant populations may serve complementary functions. The former are more numerous and may be more efficient vehicles promoting plasmid spread, while persister subpopulations guarantee plasmid reservoir maintenance even if the reservoir lacks appropriate resistance genes. Overall, our proof of principle data indicates that luminal antibiotic degradation and shuttling between the gut lumen and tissue-resident reservoirs can promote the accumulation and spread of plasmids within a host over time.


2021 ◽  
Author(s):  
Mohamad Raieszadeh ◽  
mohamad ali khosravi ◽  
Niloofar Sabzi ◽  
Davoud Esmaeili

Abstract BackgroundOne of the most resistant important mechanisms against beta-lactam antibiotics is Extended-spectrum beta-lactamase. These enzymes can hydrolyze penicillin, cephalosporin, Cephamycin, and monobactam. The genes of these enzymes are located on integron and can be transmitted to other strains of bacteria, including the Enterobacteriaceae.The study of ESBL genes is critical for the report to clinicians for an appropriate antibiotic pattern. This study aimed for rapid and precise identification of ESBL genes by the Multiplex PCR method.Methods In this study, three pair primers were designed for common ESBL genes (TEM, AmpC, KPC) using Genscript software. The first use contains control positive genes was performed set-up of PCR. Negative control samples and the 50 isolates of the Escherichia coli isolated from Baqiyatallah hospital were studied with this method. Results The results of this research showed that primers designed for ESBL genes (TEM, AmpC, KPC) were able to simultaneously identify positive control samples. The sensitivity of the multiplex PCR technique for ESBL genes was 1 pg and specificity reported 100%.Conclusion This study showed that a Multiplex PCR designed with a sensitivity of 1 pg and 100% specificity can correctly detect ESBL genes. Therefore, by quickly and correctly identifying the pattern of antibiotic resistance and providing a suitable treatment pattern to physicians, the spread of antibiotic resistance genes as well as the occurrence of economic and human losses can be prevented.


Author(s):  
Shawnm Ahmed Aziz

Antibiotic resistance has become a major world health challenge and has limited the ability of physician's treatment. Staphylococcus aureus the most notorious pathogens causes morbidity and mortality especially in burn patients. However, Staphylococcus aureus rapidly acquired resistance to multiple antibiotics. Vancomycin, a glycopeptide antibiotic remains a drug of choice for treatment of severe Methicillin Resistance S. aureus infections. This study aimed to detect the emergence of beta-lactam and glycopeptide resistance genes. 50 clinical specimens of S. aureus collected from burn patients in burn and plastic surgery units in Sulaimani-Iraq city. All specimens were confirmed to be positive for S. aureus. All the isolates were assessed for their susceptibility to different antibiotics depending on NCCL standards, followed by Extended Spectrum Beta Lactamase detection by double disk diffusion synergy test. The production of β- lactamases was evaluated in the isolated strains by several routine methods and polymerase chain reaction. Among the isolates 94% were Methicillin resistance and 34.28% were Extended Spectrum Beta Lactamase producer. PCR based molecular technique was done for the bla genes related to β- lactamase enzymes by the specific primers, as well as genes which related to reduced sensitivity to Vancomycin were detected. The results indicated that all isolated showed the PBP1, PBP2, PBP3, PBP4, trfA and trfB, graSR, vraS except the vraR gene and the prolonged therapy of Methicillin resistance infection with teicoplanin have been associated with progress of resistance and the rise of tecoplanin resistance may be a prologue to evolving Vancomycin resistance. In conclusion, beta-lactam over taking can rise Vancomycin- Intermediate S. aureus strains leading to appearance of Vancomycin resistance although the treatment of Vancomycin resistant infections is challenging.


Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 378
Author(s):  
Inka Marie Willms ◽  
Maja Grote ◽  
Melissa Kocatürk ◽  
Lukas Singhoff ◽  
Alina Andrea Kraft ◽  
...  

Antibiotic resistance genes (ARGs) in soil are considered to represent one of the largest environmental resistomes on our planet. As these genes can potentially be disseminated among microorganisms via horizontal gene transfer (HGT) and in some cases are acquired by clinical pathogens, knowledge about their diversity, mobility and encoded resistance spectra gained increasing public attention. This knowledge offers opportunities with respect to improved risk prediction and development of strategies to tackle antibiotic resistance, and might help to direct the design of novel antibiotics, before further resistances reach hospital settings or the animal sector. Here, metagenomic libraries, which comprise genes of cultivated microorganisms, but, importantly, also those carried by the uncultured microbial majority, were screened for novel ARGs from forest and grassland soils. We detected three new beta-lactam, a so far unknown chloramphenicol, a novel fosfomycin, as well as three previously undiscovered trimethoprim resistance genes. These ARGs were derived from phylogenetically diverse soil bacteria and predicted to encode antibiotic inactivation, antibiotic efflux, or alternative variants of target enzymes. Moreover, deduced gene products show a minimum identity of ~21% to reference database entries and confer high-level resistance. This highlights the vast potential of functional metagenomics for the discovery of novel ARGs from soil ecosystems.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S460-S461
Author(s):  
Daniel Muleta ◽  
Cullen Adre ◽  
Benji-Byrd Warner

Abstract Background The increasing spread of drug resistant gram-negative organisms is one of the major public health challenges. ESBL-producing Enterobacteriaceae has become the most common multi drug resistant pathogen in the last three decades. These organisms confer resistance to most beta-lactam antibiotics, including penicillins, third generation cephalosporins, monobactams and tazobactam. Methods The Tennessee Health Department (TDH) collaborated with CDC to pilot population based surveillance of ESBL producing organisms in Maury, Wayne, Lewis and Marshall Counties during October to December 2017. A case was defined as isolation of Escherichia coli, Klebsiella pneumoniae, or Klebsiella oxytoca resistant to at least one extended-spectrum cephalosporin (ceftazidime, cefotaxime or ceftriaxone) and non-resistant to all carbapenem antibiotics from urine or normally sterile body sites from a resident of the surveillance catchment area. A line list of ESBL-producing organisms was received from the labs that serve the catchment population. Case report forms were completed for the first ESBL culture collected from a single patient in a 30 day-period. Results A total of 154 cases were identified during the study period. E.coli constitutes 92.2% of the ESBL producing organisms followed by Klebsiella pneumonia (5.2%) and K. oxytoca (2.6%). The estimated annual incidence rate was 400.7 per 100,000 population which is more than twice of the average rates of other sites that conducted similar studies. The most common isolate source was urine (97%), and 81.2% of all cases were female. Patient ages ranged from 3-99 years, with average of 67 years. Thirty-two isolates underwent additional sequence typing and 76.7% (23) of the isolates were ST 131. 21 (91.3%) of ST-131 isolates were resistant to ciprofloxacin. Conclusion The study revealed that the incidence of ESBL producing organisms is very high in the Tennessee study area compared to other sites. The most common ESBL-producing pathogen was found to be ST 131 and most of these were resistant to ciprofloxacin suggesting that resistance to fluoroquinolone may be co-transmitted in ESBL producing pathogens through plasmids. Continued surveillance of molecular epidemiology is important to guide the prevention of the spread of drug resistant pathogens. Disclosures All Authors: No reported disclosures


1995 ◽  
Vol 39 (10) ◽  
pp. 2258-2261 ◽  
Author(s):  
S. Haghgoo ◽  
T. Hasegawa ◽  
M. Nadai ◽  
L. Wang ◽  
T. Nabeshima ◽  
...  

2003 ◽  
Vol 77 (9) ◽  
pp. 661-666 ◽  
Author(s):  
Yoshio YAMAGUCHI ◽  
Hideaki HANAKI ◽  
Kazunari BARADA ◽  
Takashi INAMATSU ◽  
Keisuke SUNAKAWA

1981 ◽  
Vol 20 (1) ◽  
pp. 38-46 ◽  
Author(s):  
B Slocombe ◽  
M J Basker ◽  
P H Bentley ◽  
J P Clayton ◽  
M Cole ◽  
...  

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