With rising numbers of drug-resistant Acinetobacter baumannii cases worldwide, we urgently need to better understand its virulence mechanisms. Lactate metabolism seems to be a key virulence trait of not only A. baumannii but also other human pathogens. The study “Lactate metabolism promotes in vivo fitness during Acinetobacter baumannii infection” in FEMS Microbiology Letters investigates the impact of the lactate permease on this pathogen’s virulence strategy, as discussed by Faye Morris in this #FEMSmicroBlog. #FascinatingMicrobes
Acinetobacter baumannii – a deadly pathogen
As a Gram-negative opportunistic pathogen, Acinetobacter baumannii causes a diverse range of infections, the most prevalent being bacteraemia and pneumonia. This particular pathogen affects vulnerable members of society; including those who are immunocompromised and/or in ICU, with resultant crude mortality rates between 24 and 83%.
In recent years, A. baumannii notoriety increased due to the rapid and global dissemination of antibiotic-resistant lineages. As a result, the World Health Organisation considers carbapenem-resistant A. baumannii one of the pathogens of critical priority, urgently requiring new therapeutic options.
In contrast to other Gram-negative pathogens, A. baumannii encodes only a few traditional virulence factors. However, large portions of its genome have not been functionally characterised.
This lack of information has hindered efforts to understand the virulence and physiological factors critical to its success in vivo. Previous research showed that during mammalian systemic infection, the lactate metabolism locus of this pathogen is upregulated. That’s why the study “Lactate metabolism promotes in vivo fitness during Acinetobacter baumannii infection” in FEMS Microbiology Letters characterised the role of the lactate permease in a clinical strain.
Understanding the impact of lactate on the host and the pathogen
Lactate is a biologically important molecule for both humans and bacteria. It is found in two steric forms in Nature: D- and L-. While D-(-)-lactate is only detected at nanomolar concentrations, L-(+)-lactate is far more prevalent, at 1-2 mmol/L in normal human serum.
Accordingly, lactate is an important and abundant carbon source for both the host and the pathogen. But in the host, it also functions as a key signalling component. As such, lactate is associated with modulating pro- and anti-inflammatory immune responses, recruiting immune cells and evading the immune response.
During severe sepsis, serum L-lactate levels can escalate rapidly to ≥ 8 mmol/L. Therefore, it is considered an important marker for sepsis prognosis.
Lactate utilisation promotes immune evasion
The study showed that A. baumannii encodes only one single lactate metabolism locus. By disrupting the lactate permease, encoded by lldP, bacteria lose their fitness in a murine model of systemic infection. Hence, to use lactate as a carbon source for growth, A. baumannii requires the permease.
Interestingly, in several other pathogens, including Neisseria and Hemophilus, metabolising lactate provides more than just carbon for the cell to grow. Lactate degradation also helps the bacterium evade immune attacks. By modifying the bacterial outer membrane and depleting phagocyte’s intracellular oxygen concentrations, lactate metabolites confer resistance to complement-mediated killing and reactive oxygen burst.
Based on this similarity, A. baumannii were cultured with physiologically relevant concentrations of lactate, which enhanced bacterial survival in healthy human blood. In comparison, human blood killed mutants lacking the permease. These results confirmed that, similar to other pathogens, in A. baumannii, lactate metabolism promotes immune evasion via the lactate permease.
The mechanistic details of how lactate metabolism contributes to pathogenesis and immune evasion in A. baumannii have yet to be fully elucidated. Since similar results were observed in other key pathogens, lactate metabolism might be a conserved mechanism exploited by pathogens for their survival and success in vivo. Hence, this study highlights the importance of understanding the biochemical and biological roles of lactate in the context of mammalian infections.
- Read the article “Lactate metabolism promotes in vivo fitness during Acinetobacter baumannii infection” by et al. in FEMS Microbiology Letters (2024).
Faye Morris completed her Ph.D. at the University of Birmingham, UK and pursues a postdoc position at Monash University, Melbourne, Australia. Working with Prof. Anton Peleg, she seeks to understand the molecular mechanisms that contribute to the success of Acinetobacter baumannii as a pathogen. To understand the delicate interplay between host and pathogen, they are identifying unique factors contributing to virulence.
About this blog section
The section #FascinatingMicrobes for the #FEMSmicroBlog explains the science behind a paper and highlights the significance and broader context of a recent finding. One of the main goals is to share the fascinating spectrum of microbes across all fields of microbiology.
| Do you want to be a guest contributor? |
| The #FEMSmicroBlog welcomes external bloggers, writers and SciComm enthusiasts. Get in touch if you want to share your idea for a blog entry with us! |