A Compound Inhibits Biofilm Formation of <i>Staphylococcus aureus</i> from <i>Streptomyces</i>

Abstract

Biofilm is one virulence factor of bacteria. It contributes not only to bacterial adherence to many kinds of infection-establishing surfaces, but also to bacterial resistance against antimicrobial agents and antiseptic agents. Thus, inhibitors of bacterial biofilm formation should be useful in the prevention of infections. We found that a culture of Streptomyces sp. strain MC11024 showed inhibitory activity on biofilm formation by Staphylococcus aureus and isolated streptorubin B as an inhibitor of this formation in S. aureus. The biofilm formation of methicillin resistant S. aureus (MRSA) N315 was reduced to less than 30% at 1 µg/mL of streptorubin B, and at this concentration cell growth was not affected. Our study suggests that streptorubin B has the potential to be a leading compound of anti-infectious agents of S. aureus. Key words biofilm; inhibitor; Staphylococcus aureus; Streptomyces; prodigiosinPathogenic bacteria produce many kinds of virulence factors and cause human infectious diseases. Among them, adherence factors are important for establishing infections. 1,2)Such factors also confer adhering and staying on every surface including medical devices. One of such factors, biofilm, is a relatively flexible and sticky structure.3) Once bacteria form biofilm on the surface of medical devices set in the human body, it is difficult to remove the biofilm. It is also known that biofilm prevents the penetration of antibacterial drugs and helps bacteria escape from host immune systems. 4)Some infections correlate with biofilm formation at the clinical site. 5)Biofilm formation by bacteria starts with the production of adhering factors. Bacterial cells attach to many kinds of surfaces via electrical charge and specific interactions. After that, bacteria develop biofilm by producing high viscosity extracellular matrix including polysaccharides, proteins, DNA and so on. After the biofilm has been developed, part of the bacteria in the biofilm releases some proteases, detaching them from the biofilm, and the small block of biofilm containing bacteria moves to other places. 6) While bacteria attach to surfaces and mature biofilm, they also release many virulence factors. 7)

Antibiofilm activity of threeActinomycetestrains againstStaphylococcus epidermidis

“…; Suzuki et al . ). However, there are few documents about S. epidermidis biofilm inhibitors from Actinomycete .…”

Streptomyces ‐derived actinomycin D inhibits biofilm formation via downregulating ica locus and decreasing production of PIA in Staphylococcus epidermidis

“…; Xie et al ). Consequently, inhibitors of S. epidermidis biofilm formation are good candidates for anti‐infectious agents, as such agents should work for not only preventing attachment to surfaces but also attenuating resistance to antibiotic agents (Suzuki et al ).…”

Serratia Secondary Metabolite Prodigiosin Inhibits Pseudomonas aeruginosa Biofilm Development by Producing Reactive Oxygen Species that Damage Biological Molecules

“…The concentration of prodigiosin required to inhibit biofilm formation of P. aeruginosa was within the range of 100–500 μM, which is at least five times higher than the reported concentrations required to induce apoptosis in human cancer cell lines (da Silva Melo et al, 2000 ; Montaner et al, 2000 ; Montaner and Perez-Tomas, 2001 ) and larger than the concentration of Streptorubin B to inhibit biofilm formation (Suzuki et al, 2015 ). Prodigiosin induces apoptotic effect in cancer cell lines through regulation of apoptopic and anti-apoptotic genes (Hassankhani et al, 2014 ), while the prodigiosin mediated biofilm inhibition has shown to rely on the production of reactive oxygen species.…”

“…), has shown to be a very potent inhibitor of biofilm formation of S. aureus . However, the exact biofilm inhibitory mechanism of Streptorubin B remains unknown (Suzuki et al, 2015 ).…”