Novel Australian research has confirmed the presence of bacterial biofilm in bronchoalveolar lavage specimens from children with protracted bacterial bronchitis (PBB) or bronchiectasis. Two of the researchers, Dr Ruth Thornton and Dr Robyn Marsh, provide some insight into their study, published in The Lancet Microbe, and its implications.

Can you sum up the aim of this project in 10 words?

To determine biofilm prevalence among kids with chronic wet cough

What aspect of this research excited you the most?

Robyn: We’ve been working with Professor Anne Chang for a while now to understand the microbiology underlying chest infections in kids with PBB or bronchiectasis. Recurrent chest infections are a hallmark of these conditions, even when kids are treated with antibiotics that should work. Being able to partner with Ruth and her team in WA to do this work was terrifically exciting as it meant we could determine whether these kids have biofilm-associated infections. Understanding this is critical to working out how best to treat PBB and prevent bronchiectasis.

Ruth: I have always been excited to unravel the underlying disease pathogenesis in chronic infections that don’t respond well to standard treatments. It is the only way people will start considering alternative treatments which might be more effective. We have done this previously by demonstrating biofilm involvement in otitis media – here and here – and this has led to a clinical trial which is now underway. It would be amazing to be able to help improve treatments for lung disease as well.

What have you previously discovered in the area of biofilms?

Ruth: I previously showed that bacteria persist both in biofilms and intracellularly, in biofilm pods, in the middle ears of children who have chronic and recurrent otitis media. These act as a bacterial reservoir which are not able to be eradicated by antibiotics and these kids end up needing grommet surgery. Robyn and I also previously worked together for a pilot study that demonstrated proof-of-principle that biofilm was present in lung samples from kids with bronchiectasis but we weren’t able to determine biofilm prevalence in this study and didn’t include any kids with PBB.

BAL from a child with PBB showing a large polymicrobial biofilm positive for Moraxella catarrhalis

What do we know about how, when and why biofilms form?

Robyn: Bacteria have evolved all sorts of mechanisms that give them a survival advantage in hostile environment. We know from lab-based studies that some bacteria that cause chest infection in kids can produce biofilm, but it’s not a universal response. We don’t understand why biofilm manifests in a subset of children, but it’s likely to be triggered by a range of environmental pressures, including interactions among different bacteria or due to immune pressures. Understanding this is a focus of where our research goes next.

How long before this work might impact on patient care?

Ruth: It is hard to say, but we are hopeful that this won’t be too far away given recent advances in the development of antibiofilm therapies, including treatments that target the host-microbial interactions that are likely essential for biofilm maintenance. We already have a clinical trial for this in otitis media, and there are also promising vaccine candidates that specifically target respiratory biofilms which have the potential to be gamechangers.

What’s the current availability of specialised microscopy for biofilms?

Robyn: It’s hard to get access to these types of microscopes outside of specialist research centres. We’ve been lucky to be able to partner with Ruth and her team to do this work as this technology isn’t available in the NT where my team is based. This critical technological gap is driving where our work goes next in terms of achieving more feasible diagnostic tests. Ideally, we’d like to develop a non-invasive way of testing for biofilms among kids with PBB or bronchiectasis as current tests require the kids to undergo general anaesthesia. There has been some terrific progress made in the development of breath-based diagnostics and we are keen to explore whether breath could also be used to detect biofilm-associated infections.

How does the presence of a biofilm affect treatment strategies?

Ruth: Probably the most important thing from a treatment perspective, is that when bacteria are in biofilms they are up to a thousand times more resistant to antibiotics than the planktonic bacteria which typically cause acute infections. This can make it nearly impossible to eradicate biofilm-associated infections with standard antibiotic therapies. We don’t yet know the best way to eradicate biofilm-associated infections among kids with PBB or bronchiectasis, but there are new antibiofilm treatments emerging that may be suitable. Importantly, we know that clinical biofilms are able to hijack the host immune responses which are produced to kill them, so it’s likely that both the host and the bacterial components of these infections need to be targeted if we are to truly improve treatment outcomes.

What else do we need to know about biofilms to improve management of these infections?

Robyn: One of the other findings from our study was that we detected two types of biofilms, one of which was associated with the cell types from the oral cavity. We’re not yet sure whether these types of biofilms are important to the disease processes or whether their presence was just incidental because of the way that the lung samples were collected. We are interested in knowing more about this as animal studies have shown that chest infections caused by biofilms can be more severe and take longer to resolve than those caused by planktonic bacteria.

Ruth: It’s also important to understand the overall composition of the biofilms. While we know that there appear to be both polymicrobial and monospecies biofilms present, from a vaccine development perspective, it will be important to understand which ones are there and what they are doing in order to develop treatments which may be able to resolve established infections or prevent them to begin with in those kids which are at high risk.

What is your biggest research hurdle?

Ruth: If you ever ask a scientist what one of the biggest research hurdles is, one of the first things will always be funding, specifically for personnel and discovery research which are very challenging. Both Robyn and myself are lucky to have the trust and support of philanthropic foundations, Robyn with the Rebecca L Cooper Foundation, and previously NHMRC, and myself currently with the Garnett Passe and Rodney Williams Memorial Foundation and previously with the BrightSpark Foundation. But getting funding to do important discovery science and to support good staff is quite challenging at the moment.

Robyn: I’d echo Ruth’s comments too. Securing funding is always one of our biggest challenges. From a technical perspective, we’re also limited by reliance on lung specimens collected under general anaesthesia when kids with PBB or bronchiectasis undergo clinical bronchoscopic investigations. The lack of a non-invasive way of sampling the lungs of very young children makes it challenging to understand the earlier stages in the disease processes and to study longitudinal changes in the microbiome – both of which are critical to determining optimal clinical management.

What’s your Holy Grail – the one thing you’d like to achieve in your research career?

Ruth: To really understand the host-pathogen interplay in these respiratory biofilm infections and to develop more effective treatments, and ultimately preventative therapies  targeting biofilms so as to make a real impact on the lives of children and their families.

Robyn: The holy grail from a diagnostics perspective would be to have a non-invasive way of sampling the lungs. Being able to do this would be a game changer as it would allow us to study changes in the lung microbiome and immune responses early in the disease process and to monitor changes over time. Those types of data are likely to be critical to achieving the clinical prevention and treatment outcomes that we are all striving towards.