scholarly journals Engineered CRISPR-Cas systems for the detection and control of antibiotic-resistant infections

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuye Wu ◽  
Dheerendranath Battalapalli ◽  
Mohammed J. Hakeem ◽  
Venkatarao Selamneni ◽  
Pengfei Zhang ◽  
...  

AbstractAntibiotic resistance is spreading rapidly around the world and seriously impeding efforts to control microbial infections. Although nucleic acid testing is widely deployed for the detection of antibiotic resistant bacteria, the current techniques—mainly based on polymerase chain reaction (PCR)—are time-consuming and laborious. There is an urgent need to develop new strategies to control bacterial infections and the spread of antimicrobial resistance (AMR). The CRISPR-Cas system is an adaptive immune system found in many prokaryotes that presents attractive opportunities to target and edit nucleic acids with high precision and reliability. Engineered CRISPR-Cas systems are reported to effectively kill bacteria or even revert bacterial resistance to antibiotics (resensitizing bacterial cells to antibiotics). Strategies for combating antimicrobial resistance using CRISPR (i.e., Cas9, Cas12, Cas13, and Cas14) can be of great significance in detecting bacteria and their resistance to antibiotics. This review discusses the structures, mechanisms, and detection methods of CRISPR-Cas systems and how these systems can be engineered for the rapid and reliable detection of bacteria using various approaches, with a particular focus on nanoparticles. In addition, we summarize the most recent advances in applying the CRISPR-Cas system for virulence modulation of bacterial infections and combating antimicrobial resistance. Graphical Abstract

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 2047
Author(s):  
Magda Ferreira ◽  
Maria Ogren ◽  
Joana N. R. Dias ◽  
Marta Silva ◽  
Solange Gil ◽  
...  

Antimicrobial drugs are key tools to prevent and treat bacterial infections. Despite the early success of antibiotics, the current treatment of bacterial infections faces serious challenges due to the emergence and spread of resistant bacteria. Moreover, the decline of research and private investment in new antibiotics further aggravates this antibiotic crisis era. Overcoming the complexity of antimicrobial resistance must go beyond the search of new classes of antibiotics and include the development of alternative solutions. The evolution of nanomedicine has allowed the design of new drug delivery systems with improved therapeutic index for the incorporated compounds. One of the most promising strategies is their association to lipid-based delivery (nano)systems. A drug’s encapsulation in liposomes has been demonstrated to increase its accumulation at the infection site, minimizing drug toxicity and protecting the antibiotic from peripheral degradation. In addition, liposomes may be designed to fuse with bacterial cells, holding the potential to overcome antimicrobial resistance and biofilm formation and constituting a promising solution for the treatment of potential fatal multidrug-resistant bacterial infections, such as methicillin resistant Staphylococcus aureus. In this review, we aim to address the applicability of antibiotic encapsulated liposomes as an effective therapeutic strategy for bacterial infections.


2021 ◽  
Author(s):  
Lihui Yuwen ◽  
Qiu Qiu ◽  
Wei-Jun Xiu ◽  
Kaili Yang ◽  
Yuqing Li ◽  
...  

Infectious diseases associated with antibiotic-resistant bacteria are ever-growing threats to public health. Effective treatment and detection methods of bacterial infections are in urgent demand. Herein, novel phototheranostic nanoagents (MoS2@HA-Ce6 nanosheets,...


2021 ◽  
Vol 10 (16) ◽  
pp. e34101623190
Author(s):  
Débora Brito Goulart

Urinary tract infection (UTI) caused by uropathogenic Escherichia coli (UPEC) is one of the most prevalent bacterial infections and is a major cause of health-related morbidity and hospital costs worldwide. The rising bacterial resistance to routinely given antibiotics for infected individuals is becoming a significant source of concern. Current research shows that UPEC is becoming more resistant to multiple antibiotic classes, including fluoroquinolones, beta-lactams, and aminoglycosides, as a result of genetic determinants of resistance and multidrug-resistant clones. Knowledge of the local etiology and the sensitivity profile of the most common uropathogens to antibiotics should guide decisions in the empirical therapy of uncomplicated UTI. Given the high prevalence of UTI and multidrug-resistant bacteria, preventative measures such as the development of an efficient vaccination are essential. The current work is an integrated literature review that synthesizes information on UTIs caused by antibiotic-resistant uropathogenic E. coli and considers the practical implications of key research results.


mSystems ◽  
2021 ◽  
Author(s):  
Indorica Sutradhar ◽  
Carly Ching ◽  
Darash Desai ◽  
Mark Suprenant ◽  
Emma Briars ◽  
...  

The rate at which antimicrobial resistance (AMR) has developed and spread throughout the world has increased in recent years, and according to the Review on Antimicrobial Resistance in 2014, it is suggested that the current rate will lead to AMR-related deaths of several million people by 2050 (Review on Antimicrobial Resistance, Tackling a Crisis for the Health and Wealth of Nations , 2014). One major reservoir of resistant bacterial populations that has been linked to outbreaks of drug-resistant bacterial infections but is not well understood is in wastewater settings, where antibiotic pollution is often present.


2021 ◽  
Author(s):  
Inga S. Shchelik ◽  
Karl Gademann

Antibiotic-resistant and biofilm-associated infections constitute a rapidly growing issue. The last resort antibiotic vancomycin is under threat, due to the increasing appearance of vancomycin resistant bacteria as well as the formation of biofilms. Herein, we report a series of novel vancomycin derivatives carrying thiol- and disulfide-containing moieties. The new compounds exhibited enhanced antibacterial activity against a broad range of bacterial strains, including vancomycin resistant microbes and Gram-negative bacteria. Moreover, all obtained derivatives demonstrated improved antibiofilm formation activity against VanB resistant Enterococcus compared to vancomycin. This work established a promising strategy for combating drug-resistant bacterial infections or disrupting biofilm formation and advances the knowledge on structural optimization of antibiotics with sulfur-containing modifications.


2016 ◽  
Vol 37 (4) ◽  
pp. 173 ◽  
Author(s):  
Monica M Lahra ◽  
Jo-Anne R Dillon ◽  
CR Robert George ◽  
David A Lewis ◽  
Teodora E Wi ◽  
...  

The threat of antimicrobial resistance (AMR) in bacteria has been escalated to a rightful seat on the global health agenda. In September 2016, for only the fourth time in United Nations (UN) history, the UN General Assembly in New York will meet to focus on a health threat – antimicrobial resistance. Other diseases afforded this level of consultation at the UN were human immunodeficiency virus (HIV), non-communicable diseases and Ebola virus. There are grim predictions for the future in terms of AMR and health security that span income settings. These predictions challenge the premise that minor bacterial infections of childhood are innocuous, and threaten to halt the medical advancements dependant on antibiotic therapy. Those with compromised immune systems, whether endogenous or induced, will be at highest risk. The development and spread of AMR has been, and will continue to be, fanned by the relentless selection pressure of exposure to antibiotics whether used appropriately, unnecessarily or suboptimally, in human health, animal health and agriculture. The distribution of antibiotic resistant bacteria is facilitated by travel and transport. Antimicrobial resistance will affect those in the community and the hospital.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yan Yong ◽  
Yanhong Zhou ◽  
Kexin Liu ◽  
Guochang Liu ◽  
Liqin Wu ◽  
...  

Antibiotic resistance is an increasing concern for human and animal health worldwide. Recently, the concept of reverting bacterial resistance by changing the metabolic state of antibiotic-resistant bacteria has emerged. In this study, we investigated the reversal of Apramycin resistance in Salmonella. First, non-targeted metabonomics were used to identify key differential metabolites of drug-resistant bacteria. Then, the reversal effect of exogenous substances was verified in vivo and in vitro. Finally, the underlying mechanism was studied. The results showed that the metabolites citrulline and glutamine were significantly reduced in Apramycin-resistant Salmonella. When citrulline and glutamine were added to the culture medium of drug-resistant Salmonella, the killing effect of Apramycin was restored markedly. Mechanistic studies showed that citrulline and glutamine promoted the Tricarboxylic acid cycle, produced more NADH in the bacteria, and increased the proton-motive force, thus promoting Apramycin entry into the bacterial cells, and killing the drug-resistant bacteria. This study provides a useful method to manage infections by antibiotic-resistant bacteria.


2015 ◽  
Vol 78 (4) ◽  
pp. 760-766 ◽  
Author(s):  
A. KILONZO-NTHENGE ◽  
A. BROWN ◽  
S. N. NAHASHON ◽  
D. LONG

Antibiotic-resistant bacteria existing in agricultural environments may be transferred to humans through food consumption or more multifaceted environmental paths of exposure. Notably, enterococcal infections are becoming more challenging to treat as their resistance to antibiotics intensifies. In this study, the prevalence and antibiotic resistance profiles of enterococci in organic and conventional chicken from retail stores were analyzed. Of the total 343 retail chicken samples evaluated, 282 (82.2%) were contaminated with Enterococcus spp. The prevalence was higher in organic chicken (62.5%) than conventional chicken (37.5%). Enterococcus isolates were submitted to susceptibility tests against 12 antimicrobial agents. Among the isolates tested, streptomycin had the highest frequencies of resistance (69.1 and 100%) followed by erythromycin (38.5 and 80.0%), penicillin (14.1 and 88.5%), and kanamycin (11.3 and 76.9%) for organic and conventional isolates, respectively. Chloramphenicol had the lowest frequency (0.0 and 6.6%, respectively). The predominant species in raw chicken was E. faecium (27.3%), followed by E. gallinarum (6.0%), E. casseliflavus (2.1%), and E. durans (1.4%). These species were also found to be resistant to three or more antibiotics. The data indicated that antibiotic-resistant enterococci isolates were found in chicken whether it was organic or conventional. However, enterococci isolates that were resistant to antibiotics were less common in organic chicken (31.0%) when compared with those isolated from conventional chicken (43.6%). The results of this study suggest that raw retail organic and conventional chickens could be a source of antibiotic-resistant enterococci.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Feng Gao ◽  
Tianyi Shao ◽  
Yunpeng Yu ◽  
Yujie Xiong ◽  
Lihua Yang

AbstractActing by producing reactive oxygen species (ROS) in situ, nanozymes are promising as antimicrobials. ROS’ intrinsic inability to distinguish bacteria from mammalian cells, however, deprives nanozymes of the selectivity necessary for an ideal antimicrobial. Here we report that nanozymes that generate surface-bound ROS selectively kill bacteria over mammalian cells. This result is robust across three distinct nanozymes that universally generate surface-bound ROS, with an oxidase-like silver-palladium bimetallic alloy nanocage, AgPd0.38, being the lead model. The selectivity is attributable to both the surface-bound nature of ROS these nanozymes generate and an unexpected antidote role of endocytosis. Though surface-bound, the ROS on AgPd0.38 efficiently eliminated antibiotic-resistant bacteria and effectively delayed the onset of bacterial resistance emergence. When used as coating additives, AgPd0.38 enabled an inert substrate to inhibit biofilm formation and suppress infection-related immune responses in mouse models. This work opens an avenue toward biocompatible nanozymes and may have implication in our fight against antimicrobial resistance.


Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 571
Author(s):  
Nicole Zacharias ◽  
Iris Löckener ◽  
Sarah M. Essert ◽  
Esther Sib ◽  
Gabriele Bierbaum ◽  
...  

Bacterial infections have been treated effectively by antibiotics since the discovery of penicillin in 1928. A worldwide increase in the use of antibiotics led to the emergence of antibiotic resistant strains in almost all bacterial pathogens, which complicates the treatment of infectious diseases. Antibiotic-resistant bacteria play an important role in increasing the risk associated with the usage of surface waters (e.g., irrigation, recreation) and the spread of the resistance genes. Many studies show that important pathogenic antibiotic-resistant bacteria can enter the environment by the discharge of sewage treatment plants and combined sewage overflow events. Mussels have successfully been used as bio-indicators of heavy metals, chemicals and parasites; they may also be efficient bio-indicators for viruses and bacteria. In this study an influence of the discharge of a sewage treatment plant could be shown in regard to the presence of E. coli in higher concentrations in the mussels downstream the treatment plant. Antibiotic-resistant bacteria, resistant against one or two classes of antibiotics and relevance for human health could be detected in the mussels at different sampling sites of the river Rhine. No multidrug-resistant bacteria could be isolated from the mussels, although they were found in samples of the surrounding water body.


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