Involvement of the Iron-Regulated Loci hts and fhuC in Biofilm Formation and Survival of Staphylococcus epidermidis within the Host
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Involvement of the Iron-Regulated Loci hts and fhuC in Biofilm Formation and Survival of Staphylococcus epidermidis within the Host. / Oliveira, Fernando; Lima, Tânia; Correia, Alexandra; Silva, Ana Margarida; Soares, Cristina; Morais, Simone; Weißelberg, Samira; Vilanova, Manuel; Rohde, Holger; Cerca, Nuno.
In: MICROBIOL SPECTR, Vol. 10, No. 1, e0216821, 23.02.2022.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Involvement of the Iron-Regulated Loci hts and fhuC in Biofilm Formation and Survival of Staphylococcus epidermidis within the Host
AU - Oliveira, Fernando
AU - Lima, Tânia
AU - Correia, Alexandra
AU - Silva, Ana Margarida
AU - Soares, Cristina
AU - Morais, Simone
AU - Weißelberg, Samira
AU - Vilanova, Manuel
AU - Rohde, Holger
AU - Cerca, Nuno
PY - 2022/2/23
Y1 - 2022/2/23
N2 - Staphylococcus epidermidis is a major nosocomial pathogen with a remarkable ability to persist on indwelling medical devices through biofilm formation. Nevertheless, it remains intriguing how this process is efficiently achieved under the host's harsh conditions, where the availability of nutrients, such as essential metals, is scarce. Following our previous identification of two iron-regulated loci putatively involved in iron transport, hts and fhuC, we assessed here their individual contribution to both bacterial physiology and interaction with host immune cells. Single deletions of the hts and fhuC loci led to marked changes in the cell iron content, which were partly detrimental for planktonic growth and strongly affected biofilm formation under iron-restricted conditions. Deletion of each of these two loci did not lead to major changes in S. epidermidis survival within human macrophages or in an ex vivo human blood model of bloodstream infection. However, the lack of either hts or fhuC loci significantly impaired bacterial survival in vivo in a murine model of bacteremia. Collectively, this study establishes, for the first time, the pivotal role of the iron-regulated loci hts and fhuC in S. epidermidis biofilm formation and survival within the host, providing relevant information for the development of new targeted therapeutics against this pathogen. IMPORTANCE Staphylococcus epidermidis is one of the most important nosocomial pathogens and a major cause of central line-associated bloodstream infections. Once in the bloodstream, this bacterium must surpass severe iron restriction in order to survive and establish infection. Surprisingly, very little is known about the iron acquisition mechanisms in this species. This study represents the first report on the involvement of the S. epidermidis iron-regulated loci hts and fhuC in biofilm formation under host relevant conditions and, most importantly, in survival within the host. Ultimately, these findings highlight iron acquisition and these loci in particular, as potential targets for future therapeutic strategies against biofilm-associated S. epidermidis infections.
AB - Staphylococcus epidermidis is a major nosocomial pathogen with a remarkable ability to persist on indwelling medical devices through biofilm formation. Nevertheless, it remains intriguing how this process is efficiently achieved under the host's harsh conditions, where the availability of nutrients, such as essential metals, is scarce. Following our previous identification of two iron-regulated loci putatively involved in iron transport, hts and fhuC, we assessed here their individual contribution to both bacterial physiology and interaction with host immune cells. Single deletions of the hts and fhuC loci led to marked changes in the cell iron content, which were partly detrimental for planktonic growth and strongly affected biofilm formation under iron-restricted conditions. Deletion of each of these two loci did not lead to major changes in S. epidermidis survival within human macrophages or in an ex vivo human blood model of bloodstream infection. However, the lack of either hts or fhuC loci significantly impaired bacterial survival in vivo in a murine model of bacteremia. Collectively, this study establishes, for the first time, the pivotal role of the iron-regulated loci hts and fhuC in S. epidermidis biofilm formation and survival within the host, providing relevant information for the development of new targeted therapeutics against this pathogen. IMPORTANCE Staphylococcus epidermidis is one of the most important nosocomial pathogens and a major cause of central line-associated bloodstream infections. Once in the bloodstream, this bacterium must surpass severe iron restriction in order to survive and establish infection. Surprisingly, very little is known about the iron acquisition mechanisms in this species. This study represents the first report on the involvement of the S. epidermidis iron-regulated loci hts and fhuC in biofilm formation under host relevant conditions and, most importantly, in survival within the host. Ultimately, these findings highlight iron acquisition and these loci in particular, as potential targets for future therapeutic strategies against biofilm-associated S. epidermidis infections.
U2 - 10.1128/spectrum.02168-21
DO - 10.1128/spectrum.02168-21
M3 - SCORING: Journal article
C2 - 35019768
VL - 10
JO - MICROBIOL SPECTR
JF - MICROBIOL SPECTR
SN - 2165-0497
IS - 1
M1 - e0216821
ER -