Do Mixed-Species Biofilms Dominate in Chronic Infections?–Need for in situ Visualization of Bacterial Organization

Abstract

Chronic infections present a serious economic burden to health-care systems. The severity and prevalence of chronic infections are continuously increasing due to an aging population and an elevated number of lifestyle related diseases such as diabetes. Treatment of chronic infections has proven difficult, mainly due to the presence of biofilms that render bacteria more tolerant toward antimicrobials and the host immune response. Chronic infections have been described to harbor several different bacterial species and it has been hypothesized that microscale interactions and mixed-species consortia are present as described for most natural occurring biofilms i.e., aquatic systems and industrial settings, but also for some commensal human biofilms i.e., the mouth microbiota. However, the presence of mixed-species biofilms in chronic infections is most often an assumption based on culture-based methods and/or by means of molecular approaches, such as PCR and sequencing performed from homogenized bulk tissue samples. These methods disregard the spatial organization of the bacterial community and thus valuable information on biofilm aggregate composition, spatial organization, and possible interactions between different species is lost. Hitherto, only few studies have made visual in situ presentations of mixed-species biofilms in chronic infections, which is pivotal for the description of bacterial composition, spatial distribution, and interspecies interaction on the microscale. In order for bacteria to interact (synergism, commensalism, mutualism, competition, etc.) they need to be in close proximity to each other on the scale where they can affect e.g., solute concentrations. We argue that visual proof of mixed species biofilms in chronic infections is scarce compared to what is seen in e.g., environmental biofilms and call for a debate on the importance of mixed-species biofilm in chronic infections.

The discovery of bacterial biofilm in patients with muscle invasive bladder cancer

“…While the aforementioned methods are valid, they do not investigate the in situ presentation of bacteria in relation to human cells. As in our study, the visualization of the bacterial spatial organization in both healthy and cancer tissue, the application of species or at least genus-specific FISH is also needed in future studies (11). It is important to consider, whether the selected bladder tissue samples are representative for the bacterial communities that might reside in the bladder and this might indicate why only two of ten samples presented with bacterial aggregates.…”

Immunometabolism in biofilm infection: lessons from cancer

“…It may manifest itself as a chronic (ongoing) condition, similar to diabetes or cardiovascular disease. When it comes to some cancer types, such as ovarian cancer, chronic leukemias, and certain lymphomas, this is often the case (Harley et al 2012 ; Markman 2011 ) Biofilms have long been recognized as the main cause of most chronic diseases, including osteomyelitis, rhinosinusitis, otitis, diabetic foot ulcers, chronic wounds in general, cystic fibrosis patients' chronic pneumonia, and implants, but are not restricted to these diseases (Kvich et al 2020 ) Metastasis (Spread) One of the last stages of the tumor is metastasis Many tumor cells lose the adhesion molecules that promote stickiness and can disconnect and migrate via the circulation and lymphatic system to other human body parts (Wittekind and Neid 2005 ) Malignant cells enter the circulation or lymphatic system at this step and migrate to a different place in the body, wherein they continue to divide and establish the basis for additional tumors Although a biofilm is frequently characterized as a "cozy home" in which inhabitant bacteria are sheltered from attack, bacteria may rupture their biofilm connections and escape to colonies other surroundings. This controlled process, known as biofilm dispersion, is found in a broad range of species and is initiated in response to some biological and environmental stimuli (Guilhen et al 2017 ) Treatment method A hallmark of cancer therapy is the combination of two or more medicinal drugs that mainly target cancer-promoting or cell-sustaining processes (Bayat Mokhtari et al 2017 ) Furthermore, combination treatment may be responsible for preventing deleterious impact on cell cells while causing cytotoxic activity on tumor cells.…”

We Are One: Multispecies Metabolism of a Biofilm Consortium and Their Treatment Strategies

“…Biofilms are often comprised of multiple microbial species, each carrying its own unique features, imparting certain evolved and unique functions that are not present in their mono-species counterparts ( Flemming et al, 2016 ). Such biofilms, referred to as the multispecies biofilms, are commonly found on a wide range of medical devices and are associated with a significant amount of human bacterial infections, posing a serious human health concern and economic burden to the health-care systems ( Bryers, 2008 ; Hall et al, 2014 ; Kvich et al, 2020 ).…”