# Biology and Regulation of Staphylococcusococcal Biofilm
## 9 Staphylococcal Biofilm in the Clinical Situation  
At the end of the 1990s in the United States, experts estimated that biofilms were associated with 65% of nosocomial infections and that the annual cost of treatment of these biofilm-associated infections was higher than USD 1 billion [2; 128]. _S. aureus_ and other staphylococci are frequently found on implanted materials such as catheters, hip prosthesis, or surgical materials [5; 25; 129; 130]. A recent study identified methicillin-resistant coagulase negative staphylococci as a major cause of biofilm-associated infections and possibly responsible for critical clinical situations. This interesting study relied on the analysis of numerous samples originating from hospital environments and from various hospital wards. The authors identified different staphylococcal species that produce bacterial biofilms: _Staphylococcus haemolyticus_, _S. epidermidis_, _S. homitis_, and _S. warneri_. The authors isolated approximately 300 MR-CoNS among the 558 samples from community and hospital environments. _S. haemolyticus_ and _S. epidermidis_ were the predominant species, representing roughly 73% of the CoNS identified. Significant biofilm production was detected in 91% of isolates, suggesting that the absence of production is marginal in clinical and environmental CoNS [131]. The staphylococci isolates that were derived from hospital wards were more associated with biofilm production than the community-derived isolates. Distinguished  
Figure 4: Biofilm matrix and metabolism. (**A**) Scanning electron microscopy (SEM), of _S. epidermidis_. The cells grown for 24 h on a cellulose acetate surface show closely packed bacterial cells embedded in a slimy matrix [125]. The cells are embedded in many layers in this biofilm. The bacterial cells multiply upwards from the adherent cells and are surrounded by a layer of mucus to create a multilayer coating (biofilm). The picture shows a cross-section of this biofilm. At the perfused surface, the pH is neutral and nutrients and oxygen are present. However, towards the layers below, the oxygen, nutrients, and pH decrease continuously, forming gradients. It can be assumed that the cells permanently adapt to the changed conditions and released metabolites. (**B**) Schematic representation of formate metabolism in _S. aureus_ biofilms. In the anaerobic layers (red) of the mature biofilm, the PFL converts pyruvate to acetyl-CoA and formate. The latter can be used by strictly anaerobically grown cells for the synthesis of formyl-THF and therefore for the biosynthesis of proteins, DNA, and RNA. At the same time, formate accumulates and diffuses to microaerobic regions (light red). Here, it might be oxidized by the FDH under the production of NADH [127].  
from the isolates identified in hospital wards, environmental strains were devoid of _icaAD_ and _bap_ genes and thus produced mainly proteinaceous biofilms.  
Recent studies documented biofilms as community phenomena by assessing the interaction between bacteria and surface-associated-biofilm-producing organisms. [PERSON] reported nicely that numerous non-_aureus_ species of staphylococci were able to interact with biofilm-producing _S. aureus_. The authors isolated _S. chromogenes_, _S. epidermidis_, and _S. simulans_ from bovine milk samples and showed that _S. chromogenes_ (devoid of _ica_) stimulates the biofilm formation of _S. aureus_ and alters the dispersion of _S. aureus_-formed biofilm. The study highlighted possible interactions between CoNS and _S. aureus_ in the biofilm communities, most likely through interactions between the respective _agr_ quorum systems [132]. Further research is needed to study bacterial biofilms as community phenomena.