Vaccination

Mechanisms And Strategies To Overcome Antibiotic Resistance In Gastrointestinal Pathogens

In the field of infectious diseases, antibiotic resistance in gastrointestinal infections represents a critical challenge. Such infections, driven by pathogens like Salmonella, Escherichia coli, and Campylobacter, not only cause severe illnesses but also contribute significantly to morbidity due to their resistance to standard treatments. The evolution of antibiotic-resistant bacteria is exacerbated by the indiscriminate use of antibiotics in healthcare and agriculture, hindering effective treatment regimens and facilitating the spread of resistant strains via multiple vectors including contaminated food and water.This research topic aims to delve into the complexities of diagnosing antibiotic-resistant infections with precision, and to spearhead the creation of innovative management tools. It seeks to scrutinize the efficacy of existing diagnostic practices and develop novel methodologies for the timely detection and monitoring of such infections. Furthermore, the research intends to investigate groundbreaking strategies for treating antibiotic-resistant infections, including the synthesis of new antimicrobial agents, the application of stringent infection control protocols, and leveraging computational models to uncover novel therapeutic candidates.To gather further insights into the mechanisms and treatment of antibiotic-resistant gastrointestinal infections, we welcome articles addressing, but not limited to, the following themes:

-Research on isolation, identification, and characterization of strains causing gastrointestinal diseases with a multiresistant profile.-Identification and characterization of mechanisms of resistance.-No-drugs alternatives for the treatment of multiresistant infections (i.E., probiotics, natural compounds, bacteriophages).-In silico discovery of new antimicrobial drugs.-Pangenome characterization of multiresistant organisms.-Multiresistant organisms from both animals and humans.

Keywords: Gastrointestinal infections, Multidrug resistant bacteria, Antibiotics, in silico, Human gastrointestinal infections, Animal gastrointestinal infections

Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

In the field of infectious diseases, antibiotic resistance in gastrointestinal infections represents a critical challenge. Such infections, driven by pathogens like Salmonella, Escherichia coli, and Campylobacter, not only cause severe illnesses but also contribute significantly to morbidity due to their resistance to standard treatments. The evolution of antibiotic-resistant bacteria is exacerbated by the indiscriminate use of antibiotics in healthcare and agriculture, hindering effective treatment regimens and facilitating the spread of resistant strains via multiple vectors including contaminated food and water.This research topic aims to delve into the complexities of diagnosing antibiotic-resistant infections with precision, and to spearhead the creation of innovative management tools. It seeks to scrutinize the efficacy of existing diagnostic practices and develop novel methodologies for the timely detection and monitoring of such infections. Furthermore, the research intends to investigate groundbreaking strategies for treating antibiotic-resistant infections, including the synthesis of new antimicrobial agents, the application of stringent infection control protocols, and leveraging computational models to uncover novel therapeutic candidates.To gather further insights into the mechanisms and treatment of antibiotic-resistant gastrointestinal infections, we welcome articles addressing, but not limited to, the following themes:

-Research on isolation, identification, and characterization of strains causing gastrointestinal diseases with a multiresistant profile.-Identification and characterization of mechanisms of resistance.-No-drugs alternatives for the treatment of multiresistant infections (i.E., probiotics, natural compounds, bacteriophages).-In silico discovery of new antimicrobial drugs.-Pangenome characterization of multiresistant organisms.-Multiresistant organisms from both animals and humans.

Keywords: Gastrointestinal infections, Multidrug resistant bacteria, Antibiotics, in silico, Human gastrointestinal infections, Animal gastrointestinal infections

Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Using Good Bacteria To Eliminate Nasty Germs In The Gut

Balance must be maintained among the trillions of microbes that live in the gastrointestinal tract. The gut microbiome has to host enough beneficial microbes to help control the levels of potentially harmful bacteria that can cause gut infections, like pathogenic strains of E. Coli and Klebsiella. These pathogenic microbes are often found in hospitals. Some patients have to take extended courses of antibiotics, and these medications can harm the good microbes in the gut, leaving a door open for opportunistic germs to cause serious infections. Once those infections are established they can be difficult to eliminate because many pathogens are now resistant to different drugs.

One potential option for the treatment of antibiotic-resistant gut infections is a fecal microbiota transplant, in which the gut microbes from a healthy donor are transferred to a patient with a gut infection. Unfortunately, these treatments do not always work, and the composition of the donor sample may vary considerably. This has made it challenging to identify the most beneficial microbes in these samples (which may also vary from one patient to another).

Scientists have now aimed to learn more about the bacterial strains that are most likely to benefit patients with gut infections. In this study, the researchers analyzed forty strains of bacteria from the stool samples of five healthy donors.

In a mouse model of Klebsiella infection, eighteen of these strains were beneficial and could reduce the growth of pathogenic Klebsiella bacteria; they changed the activity of genes related to the metabolism and absorption of carbohydrates. Suggesting that the gut microbes began to compete for nutrients. The eighteen strains outcompeted the pathogens for nutrients, which harmed the pathogens' ability to proliferate in the gut. This work also revealed that the eighteen strains reduced gut inflammation in the mouse model.

The findings have been reported in Nature, and may help scientists develop more effective treatments for gut infections that may not involve medications. This approach could have fewer side effects and be more helpful for patients.

Although the gut microbiome has been studied for about two decades, researchers are only now starting to clearly identify the microbes that are good for the gut and the human body. "Part of the challenge is that each person's microbiome is unique. This collaborative effort allowed us to functionally characterize the different mechanisms of action these bacteria use to reduce pathogen load and gut inflammation," explained co-first study author Marie-Madlen Pust, a postdoctoral researcher at the Broad Institute of MIT and Harvard.

The investigators also assessed samples from patients with ulcerative colitis (and gut inflammation) and unaffected individuals. They determined that there were higher gluconate levels in pediatric patients with gut inflammation, which suggested that there is more gluconate available for pathogenic microbes to consume, which fuels their growth. Gluconate may, therefore, be contributing to gut inflammation. However, when the eighteen beneficial microbes are present in the gut, they can compete with infectious microbes for that gluconate and other nutrients, limiting their growth, and their harmful impacts.

The research also suggested that these eighteen strains do not interfere with the growth of other healthy gut microbes, highlighting their therapeutic potential.

More research will be needed to confirm these findings in more patients, and to develop therapeutics that can be applied in the clinic. But scientists are starting to determine how specific microbial strains can be helpful or harmful, and how we might be able to manipulate their growth to improve human health.

Sources: Broad Institute of MIT and Harvard, Nature

New Antibiotic Hits The Market To Tackle Stubborn UTIs

No doubt about it, UTIs suck. They burn, they itch, they come back just when you think you're in the clear. But for those dealing with these relentless infections, there's finally a new line of defense.

A new type of antibiotic is now available for some of the most annoying infections around. This month, the Food and Drug Administration approved Iterum Therapeutics' Orlynvah for certain kinds of urinary tract infections that aren't likely to respond to other drugs.

UTIs are some of the most common infections that people encounter, particularly women. About 60% of women in the U.S. Are estimated to experience at least one uncomplicated UTI (a UTI with no signs of structural damage or other health conditions) in their lifetime. While UTIs were once easily treatable with just about any simple course of antibiotics, many infections nowadays are resistant to at least one or more front-line drugs used against them. This added hardiness not only makes it harder to treat UTIs early before they cause more serious trouble, but also increases the risk of having recurrent UTIs. So scientists have been desperate to find newer antibiotics that can treat these resistant infections.

Orlynvah is the first drug of its kind. It contains a combination of sulopenem etzadroxil, which belongs to a subclass of antibacterials called penems, and probenecid, a renal tubular transport inhibitor that has been used in the past to boost the duration of antibiotics in our body. Penems are synthetic antibiotics that has shown great promise in treating a wide variety of commonly resistant germs, but Orlynvah is the first ever oral penem to be approved in the U.S.

The drug has been approved to treat certain uncomplicated UTIs caused by Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis bacteria. Importantly, Orlynvah is intended for people who have limited or no other alternative oral antibacterial options for their UTIs, such as infections that haven't responded to past treatment or infections that show clear resistance to other drugs through testing. The FDA approved Orlynvah on the basis of two Phase III trials, which found that it outperformed or matched the effectiveness of other standard antibiotics for uncomplicated UTIs, including resistant infections.

"The FDA approval of sulopenem is tremendous news for those of us who have been hoping for a new option to treat appropriate at-risk patients suffering from UTIs," said Marjorie Golden, an infectious disease specialist at the St. Raphael Campus of Yale New Haven Hospital who was involved in the drug's clinical research, in a statement from Iterum. "Based on the totality of clinical data generated, sulopenem has the potential to be an important treatment alternative for use in the community."

As valuable as Orlynvah will be for doctors and patients, the drug isn't a cure-all for UTIs in general. The drug failed to pass clinical trials testing its effectiveness against complicated UTIs or complicated intra-abdominal infections. And like many newer antibacterial drugs, its use will be carefully managed to delay the emergence of bacterial strains that evolve resistance to it.

Still, Orlynvah should be able to prevent plenty of UTI-related misery. While these infections aren't always apparent, they can cause pelvic pain, frequent and/or burning urination, and even blood in urine. Left untreated, UTIs can also raise the risk of a more serious kidney infection, a narrowed urethra in men, and even sepsis (a life-threatening inflammation that can cause widespread organ damage).

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