Our global antibiotics-resistance challenge leads us to develop new strategies to fight resistant bacteria. While novel antibiotics are being developed, investigations should also focus on how to change the therapeutic approaches of currently used antibiotics. The study “Gram-negative bacteria act as a reservoir for aminoglycoside antibiotics that interact with host factors to enhance bacterial killing in a mouse model of pneumonia” published in FEMS Microbes investigates the molecular mechanisms of such an alternative strategy. In a #BehindThePaper interview, Christiaan Wijers explains for the #FEMSmicroBlog how we can use antibiotics-loaded bacteria to fight bacterial infections.
Why is your publication important for society or non-scientists?
Both the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) state that infections caused by antibiotic-resistant bacteria pose a major threat to public health worldwide. One strategy to curb this threat is to develop novel antimicrobial compounds.
However, we should also think about how we currently use antibiotics in the clinic. We have a broad arsenal of antibiotics available and preserving or expanding them may provide other valuable strategies to fight antibiotic resistance.
Why did you choose to dive into the topic of this paper? What fascinates you about the antibiotic resistance mechanisms of bacteria?
Our group was already involved in this topic when we challenged mice with multiple pathogens that cause pneumonia. At the same time, we exposed bacteria to aminoglycosides and gave these bacteria to the infected mice. We then saw that fewer mice developed pneumonia.
The mechanism for this phenomenon was not known. Because it might have consequences for the clinical utility of aminoglycoside antibiotics, we wanted to better define the mechanisms by which this suppression of bacterial pneumonia occurred.
Can you summarise the significance of your paper for microbiologists outside of your field?
The findings presented in this manuscript indicate that Gram-negative bacteria act as a reservoir for antibiotics from the aminoglycoside class. Specifically, the negatively charged outer membrane of Gram-negative bacteria binds and retains the positively charged antibiotics. To show this, we used a mouse model of pneumonia induced by Acinetobacter baumannii.
We hypothesised that the bacteria load their membranes with the aminoglycoside and interact with antibacterial host defences. This triggers and enhances the killing of aminoglycoside-naïve, co-infecting bacteria. Therefore, in conjunction with host factors, the bacterial aminoglycoside reservoir is bioavailable to participate in bacterial killing in the lung.
These findings may provide additional insights into a novel therapy approach. Administering aminoglycoside antibiotics directly to the lungs through inhalation seems to be uniquely effective.
How could practitioners adapt your research results?
Our results help explain why aminoglycoside antibiotics appear to be so active when inhaled directly into the lung. With this approach, the antibiotics seem to remain effective even against bacteria that demonstrate an in vitro resistance to this class of antibiotics.
Thus, these findings show an alternative approach for administering aminoglycoside antibiotics. Like this, we could keep using them in the clinic to treat bacterial pneumonia.
Why did you choose the transparent peer-review process for your publication?
Peer-review is critical to both the quality and the integrity of disseminated knowledge. We reason that making the reviewers’ comments as well as our responses to those comments available to the reader provides additional context.
Kimberly Kline, editor-in-chief:
This paper was particularly interesting. The authors show that some Gram-negative bacteria can bind aminoglycosides to their exterior. This then serves as an antibiotic reservoir, or “sink”, which can later be released by surfactants encountered during infection. Consequently, this release enhances killing of the co-infecting bacteria for which this is their only antibiotic exposure.
- Read the paper “Gram-negative bacteria act as a reservoir for aminoglycoside antibiotics that interact with host factors to enhance bacterial killing in a mouse model of pneumonia” by Wijers et al. (2022) in FEMS Microbes.
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#BehindThePaper posts on the #FEMSmicroBlog aim to bring the science closer to different audiences and to tell more about the scientific or personal journey to come to the results.
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