Interleukin-1b-induced growth enhancement of Staphylococcus aureus occurs in biofilm but not planktonic cultures by McLaughlin and Hoogewerf, 2006

The interplay between biofilms and host immune system is still poorly understood.

However, in the last years several discoveries have been made that may help in the understanding of the interactions between biofilms and the host immune system response.

It seems that patients with elevated levels of cytokines develop more frequently bacterial infections. This suggests that cytokines may stimulate bacterial growth and therefore, in this paper, the authors explored the interaction between S. aureus biofilms and the some pro-inflammatory cytokines namely IL-1beta, TNF-alpha, IL-6 and MIP-alpha.

Established S. aureus biofilms were treated with the different cytokines and 6h later the biofilm biomass was determined by crystal violet staining. Planktonic cells were used as control.

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The control of death and lysis in staphylococcal biofilms: a coordination of physiological signals by Sadykov and Bayles 2012

This paper reviews the involvement of  bacterial cell death and lysis in staphylococcus biofilm development.

Previously it was found that  mutations on either cidABC or lrgAB  operons, known to be involved in cells death and lysis, results in impaired biofilm formation.

It is thought that these 2 operons encode proteins analogous to the bacteriophage-encoded holins and antiholins.

Holins (encoded by cidABC) would be responsible for bacteria cell lysis, and anti-holins (encoded by lrgAB), as the name indicates, for the inhibition of the produced holins creating, therefore, a balance between life and death.

Given the nature of the signals known to induce expression of the Cid/Lrg system, they propose that the expression of these operons are dependent on a variety of environmental conditions that exist within a biofilm, and that the metabolic variability observed within biofilms may determines the differential expression these operons through, for example, membrane potential and oxygen levels, which in turn, dictates which cells die and lyse.

This is an interesting review that explores a yet poorly understood issue of biofilm maturation and te mechanisms underlying such complex regulation.

Reference of the article summarized above:

Sadykov MR, Bayles KW (2012) “The control of death and lysis in staphylococcal biofilms: a coordination of physiological signals”. Curr Opin Microbiol.15(2): 211-215.

RM:  AF 1313

Global changes in Staphylococcus aureus gene expression in Human blood by Malachowa et al., 2011

Staphylococcus aureus is one of the leading causes of bloodstream infections worldwide, however, the mechanisms employed by the bacterium to survive in human blood, and therefore cause infection is poorly understood.

Thus, to better understand the relationship between the bacterium and the human blood, the authors have analyzed the transcriptome of the bacterium after ex vivo exposure to human blood and serum.  Additionally, they have assessed the percentage of survival of the bacterium in the human blood.

With this approach they have find:

1. After 120 minutes of exposure to human blood there were still a significant number of bacteria alive in the blood (approximately 35%).

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Immune defense against S. epidermidis biofilms: components of the extracellular polymeric substance activate distinct bactericidal mechanisms of phagocytic cells by Meyle et al., 2012

As referred before, the molecular mechanism underlying S. epidermidis biofilm formation has been extensively studied in the last years. However, when it comes to the interaction of biofilms with the host immune system effectors very little is known.

In this manuscript the authors aimed to understand the interaction between the S. epidermidis extracellular matrix and the potent phagocytic polymorphonuclear cells (PMNs). An effective phagocytic process by PMNs depends on the opsonization of the antigen by complement proteins and IgG. However, previous work developed by these authors has shown that PMNs are activated in the presence of S. epidermidis biofilms and start the phagocytic process even in the absence of opsonins, indicating that some of the biofilm matrix components may stimulate PMNs activation.

Therefore, in this study the characterization of PMNs activation by non-opsonized S. epidermidis biofilms and purified matrix fractions was performed.  Continue reading

Review of the use of statistics in Infection and Immunity by Cara H. Olsen 2003

I know that you may think that this paper is a bit off from the primary aim of this blog. However, statistics is everywhere and it is very important since our interpretation and conclusions of our data is dependent on the statistic applied.

Therefore, I have decided to share this very easy to follow paper that reviews the major errors in statistic observed in the papers published in the high standard quality Infection and Immunity journal. Since we can learn from errors, here is a brief summary of the most common errors:

1) Fail in the adjustments of the P values when doing multiple analysis.  Since the majority of the analysis performed among different groups are done independently and then taken together there is an increased probability of false significance. Therefore, an appropriated statistical test has to applied in order to compare all the groups and additionally the statistic test applied should  correct for p-values errors.

2) Several conclusions are based only in the interpretation of the dispersion of the data (such as SD or SEM). Standard deviation bars contain no information regarding the precision of the mean. In a matter of fact, it can occur considerable overlap of confidence intervals even when exist statistically significant differences between groups.

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Wake up! Peptidoglican lysis and bacterial non-growth states by Keep et al., 2006

This is an interesting review paper that discuss the mechanisms behind the activation of bacteria from protective states such as dormancy and the more controversial viable- but-not-nonculturable (VNC) state.

This protective or non-dividing states adopted by bacteria under stress are very important in clinical setting since they seem to be responsible for the development of recalcitrant infections that leads to an increased patient’s morbidity and  mortality.

Briefly, in 1998 Mukamolova et al. have introduced the concept of bacterial cytokine, characterizing the 17-kDa protein termed resuscitation-promoting factor (RPF) produced by Micrococcus luteus . Latter, it was found that this protein presented a sequence homology, despite weak, to lysosymes and lytic transglycosylase and, additionally, it was shown that  peptidoglycan is used by this protein as a substract activating, this way, cells division and the inactivation of the non-growth state.

However, much more studies have to be done to understand all the mechanisms that lead to the emergence from protective to active states of growth.

Reference of the paper summarized above:

Keep NH, Ward JM, Cohen-Gonsaud M and Henderson B. (2006)” Wake up! Peptidoglican lysis and bacterial non-growth states”. TRENDS in Microbiology 14(6): 271-276.

The biological role of death and lysis in biofilm development by Bayles 2007

This review present an interesting correlation between the programmed bacterial cell death (PCD) and the programmed eukaryotic cell death, called apoptosis. Despite the reference to several microorganisms, this paper is focused on PCD of Staphylococcus aureus and its consequence in biofilm development.

In S. aureus, the mechanisms that controls the cell death and lysis has been linked to the Cid and Lrg operons, which have an important role in the control of the murein hydrolase activity. Interestingly, the products of these genes are analogous to the bacteriophages-encoded holins and antiholins that are involved in the control of bacteriophage-mediated cell death and lysis. The role of  bacterial cell lysis in antibiotic resistance is also discussed.

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