Pathogen and drug work together to fight fungal lung infection

Date:
March 15, 2022
Source:
University of Maine
Summary:
Pathogens don't always work against drug treatments. Sometimes,
they can strengthen them, according to new research. Researchers
have now looked at two pathogens that often occur at similar sites,
particularly in cystic fibrosis and mechanically ventilated
patients: Candida albicans and Pseudomonas aeruginosa. The
researchers investigated the effectiveness of an antifungal drug,
fluconazole, with both pathogens.

The results showed that P. aeruginosa works with fluconazole to
eliminate drug tolerance and clear the C. albicans infection. The
bacteria also enhance the drug's ability against a second pathogenic
Candida species that tends to be more resistant to the drug.



FULL STORY ========================================================================== Pathogens don't always work against drug treatments. Sometimes, they
can strengthen them, according to a new University of Maine study.


========================================================================== Diseases caused by a combination of bacteria, viruses, fungi and parasites
- - also known as polymicrobial infections -- are challenging to treat
because scientists don't fully understand how pathogens interact during infection and how these interactions impact the drugs used to treat them.

In a study published in the journalInfection and Immunity, researchers in
the Molecular & Biomedical Sciences Department looked at two pathogens
that often occur at similar sites, particularly in cystic fibrosis
and mechanically ventilated patients: Candida albicans and Pseudomonas aeruginosa.

Candida is the fourth most common hospital-acquired pathogen, and is particularly difficult to treat. It is targeted by a number of antifungal agents, but some only slow it rather than kill it outright. Meanwhile, P.

aeruginosa infects 90% of all adult cystic fibrosis patients. Combined, C.

albicans and P. aeruginosa cause more serious disease in cystic fibrosis
and ventilated patients.

The researchers investigated the effectiveness of an antifungal drug, fluconazole, in the test tube and during infection of the zebrafish with
both pathogens. Fluconazole is known to slow fungal growth, but Candida
can become tolerant to the drug and not only survive, but also develop tolerance that leads to failed therapy and, potentially, death.

What the study found was promising. The results showed that P. aeruginosa
works with fluconazole to eliminate drug tolerance and clear the
C. albicans infection in the culture and the zebrafish.

"Polymicrobial infections are challenging to treat not only because
of the lack of understanding of how invading microorganisms interact
but also because we don't know how these interactions affect treatment efficacy. Our work demonstrates that polymicrobial interactions can
indeed affect treatment efficacy and, most importantly, it highlights the importance of nutrient availability in the environment -- such as iron
in our study -- and how it modulates treatment efficacy," says Siham
Hattab, lead author of the study who conducted the research as part of
her Ph.D. in the Department of Molecular and Biomolecular Sciences.

What's more, the bacteria also enhance the drug's ability against a second pathogenic Candida species that tends to be more resistant to the drug.

The increased effectiveness of the drug suggests to the researchers
that there is still much more to learn about how current drugs work
when targeting these dangerous and complex polymicrobial infections. "We
are really excited to have revealed that sometimes drugs against fungal infection can work even better in a more 'real-world' situation than in
the test tube. There is still a lot to learn about how pathogens interact during infection, and it will be interesting to see how the bacteria
manage to work with the drugs to target Candida," says Robert Wheeler, associate professor of microbiology and senior author of the study.


========================================================================== Story Source: Materials provided by University_of_Maine. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Siham Hattab, Anna-Maria Dagher, Robert T. Wheeler. Pseudomonas
Synergizes with Fluconazole against Candida during Treatment
of Polymicrobial Infection. Infection and Immunity, 2022; DOI:
10.1128/ iai.00626-21 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220315162810.htm

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