Behavioral Ecology
doi:10.1093/beheco/arl018
Advance Access publication 19 July 2006
Variable patterns of density-dependent survival
in social bacteria
Supriya V. Kadam and Gregory J. Velicer
Max-Planck-Institute for Developmental Biology, Spemannstrasse 35, D-72076 Tuebingen, Germany
In numerous species of social animals and social microorganisms, fitness is positively dependent on population density, at least in
some environments and over some density ranges. This ‘‘Allee effect’’ is observed in the cooperative bacterium Myxococcus xanthus
during multicellular fruiting body development, during which the standard laboratory genotype sporulates less efficiently at lower
population densities and produces no spores below a minimum threshold density. Here we demonstrate significant quantitative
variation in Allee patterns among distinct natural isolates of M. xanthus. Isolates with similar developmental performance at intermediate population densities exhibit stark variation in performance at both very low and very high densities. Such variation has
implications for evolutionary performance under fluctuating natural environments. It also suggests that distinct intraspecific
populations of social animals and other social microbes with different selective histories may vary in the effects of density on social
fitness. Key words: Allee effect, inverse density dependence, natural variation, social development. [Behav Ecol 17:833–838 (2006)]
ome species exhibit a positive relationship between population growth rate and population density. This concept
was first introduced by Allee et al. (1949) and is hence known
as the ‘‘Allee effect.’’ He suggested that there exist threshold
densities for some species under some conditions, below
which populations decline and thereby increase the likelihood of extinction and above which population growth rate
increases as a function of density (Courchamp, Clutton-Brock,
and Grenfell 1999; Courchamp, Grenfell, and Clutton-Brock
1999; Stephens and Sutherland 1999). The Allee effect may be
an important factor in the population ecology of many animal
and plant species and has received renewed interest in recent
decades in light of conservation and extinction concerns
(Stephens et al. 1999). More recently, the relationship between density and social performance has been highlighted
as a significant parameter in the life histories of social microorganisms as well, such as pathogens that engage in quorum
sensing of population density (Cvitkovitch et al. 2003).
A few examples exemplify the wide range of taxa in which
the Allee effect has been documented or postulated. Among
plants, for example, the grass Spartina alterniflora produces
viable seeds more efficiently in previously colonized, highdensity areas than in freshly invaded, low-density areas (Davis
et al. 2004). This effect may be due to a need for the root
systems of low-density populations to grow in close proximity
with one another before efficient seed production can occur.
Fig trees (Fiscus sp.) also suffer from low density due to decreased pollination and dispersal rates (Courchamp, CluttonBrock, and Grenfell 1999; Courchamp, Grenfell, and CluttonBrock 1999). In the animal kingdom, many species such as
African wild dogs, coyotes, and lions are obligate cooperators
that require nonreproducing helpers to assist in raising the
offspring of a few reproducers (Bekoff 1982; Packer et al.
1988; Courchamp and Macdonald 2001). By a variety of mechanisms, these species suffer decreased reproductive rate and
a higher incidence of extinction when population densities
become too low (Guo et al. 1991; Courchamp, Clutton-Brock,
and Grenfell 1999; Courchamp, Grenfell, and Clutton-Brock
S
Address correspondence to G.J. Velicer. E-mail: gregory.velicer@
tuebingen.mpg.de.
Received 17 August 2005; revised 25 May 2006; accepted 26
May 2006.
The Author 2006. Published by Oxford University Press on behalf of
the International Society for Behavioral Ecology. All rights reserved.
For permissions, please e-mail: [email protected]
1999; Thorne and Williams 1999; Wilson et al. 2002; Davis et al.
2004).
Although examples of the Allee effect have been found in
many species across a wide range of taxa, little (if any) attention has been given to the possibility of genetically based variation in quantitative Allee patterns among distinct genotypes
or populations of a single species. The existence of such variation is a necessary condition for quantitative Allee effect
patterns (i.e., the shape of a social performance curve in relation to population density) to be subject to natural selection
across distinct populations. Such variation, if it exists, may
reflect different selective pressures having affected optimal
population density across distinct evolutionary environments.
Microbial systems are being increasingly utilized to address
basic questions about the ecology and evolution of social interactions (Zahavi and Ralt 1984; Crespi 2001; Velicer 2003).
In particular, many microbes appear to exhibit advantageous
traits that require high population densities. In several bacterial species, populations in high-density biofilms are better
able to generate a coordinated protective response against
highly acidic conditions than are populations at low density
(Foster and Hall 1991; Foster 1995; Cui et al. 2001; Li et al.
2001). In pathogenic microbes such as Staphylococcus aureus,
a minimum population density is often required to initiate
expression of virulence factors needed to establish successful
infections (Ji et al. 1995). Some microbes, such as the eukaryotic slime molds and the prokaryotic myxobacteria, respond
to nutrient stress by aggregating into high-density groups that
differentiate into 3-dimensional, spore-bearing fruiting structures. In both cases, a minimum threshold density is required
to initiate development, and at least in the myxobacteria, the
efficiency of spore production tends to increase with increasing population density (Rosenbluh et al. 1989; Rietdorf et al.
1996; vanOss et al. 1996).
Here we ask whether Allee effect patterns vary significantly
across distinct natural genotypes of the social and developmental bacterium Myxococcus xanthus. Myxococcus xanthus responds to starvation by forming a fruiting body structure
within which stress-resistant spores are formed. Cell density
plays a crucial role in the initiation of fruiting body formation, with a minimum threshold density necessary to induce
the cascade of intercellular signaling leading to aggregation
(Kaiser 1996; Kaplan and Plamann 1996). The relationship
between density and sporulation efficiency in this social
Behavioral Ecology
834
bacterium might be subject to natural selection, but only if the
trait varies in a heritable manner. Specifically, the optimal
minimum group size for initiating development may vary
among distinct populations that dwell under different selective forces. For example, populations that evolve for extended
periods under low nutrient levels that only support small population sizes may be under selective pressure to evolve the
ability to undergo development at lower initial densities than
populations that normally experience more abundant resources.
On starvation, ;100 000 M. xanthus cells use directed movement to gather at high-density aggregation loci and then
cooperatively construct fruiting body structures (Shimkets
1999). The total developmental process requires cell–cell
proximity and is regulated by at least 5 stage-specific intercellular signals (Zusman 1984; Dworkin and Kaiser 1985; Shimkets
1999). A small minority (;2–5%) of the initial aggregating
population differentiates into stress-resistant spores under
standard laboratory conditions, whereas most of the remaining cells undergo autolysis (Kim and Kaiser 1990).
A density of about 3 3 108 cells/ml is required for fruiting
body formation in the standard laboratory genotype DK1622,
whereas populations below this level undergo developmental
arrest (Kaiser 1996; Kaplan and Plamann 1996). To initiate
the developmental process, cells must sense both nutrient
limitation and cell density. Two signals play a crucial role during the early preaggregation phase of development—intracellular guanosine tetra- (and penta-) phosphate ((p)ppGpp) for
nutrient limitation (Singer and Kaiser 1995) and the A-signal
for cell density (Kaplan and Plamann 1996). The A-signal is
a mix of specific amino acids, including tyrosine, proline,
tryptophan, phenylalanine, leucine, and isoleucine. When
cells detect nutrient limitation, they are thought to release
proteinases that degrade proteins on the cell surface and
thereby produce the A-signal amino acid complex. At cell
densities above 3 3 108 cells/ml, this extracellular signal exceeds the minimum threshold, and a cascade of developmentspecific gene expression is initiated.
Distinct natural isolates of M. xanthus may vary in the minimum cell density necessary to initiate development and in
the overall relationship between sporulation efficiency and
cell density. Such variation may result from adaptation to different selective conditions (e.g., variable long-term resource
levels) in soils. For example, populations that evolve under
conditions allowing only relatively small maximum population
densities may have evolved lower cell-density thresholds for
the initiation of development than populations evolving under conditions of greater average nutrient abundance.
We examined the relationship between cell density and
sporulation efficiency in 9 globally distributed natural isolates
of M. xanthus. All the isolates show a positive correlation between cell density and sporulation efficiency at low densities,
and many show decreased efficiency at very high densities.
Although these isolates are relatively similar in their developmental phenotype at intermediate densities, they exhibit stark
variation at both low and high densities. This genetically
based variation may reflect distinct selective pressures having
acted on the ability of the isolates’ ancestral lineages to initiate development at low population densities.
MATERIALS AND METHODS
Isolates
Eight natural isolates of M. xanthus were selected based on
their ability to sporulate at levels similar to the model strain
DK1622 (which is also examined in this study; Kaiser 1979)
under standard laboratory conditions and include DK836
(New York State), Mxx12C1 (Olympia, Greece), Mxx15C1
(Olympia Greece), Mxx17C1 (Minneapolis), Mxx23C1
(Minneapolis), Mxx38C1 (Madras, India), Mxx143C1 (Japan),
Mxx144C1 (Mt Ar-Li, Taiwan). Hereafter, isolates are referred
to without their clone designation (C1). Natural isolates kindly
provided by Dale Kaiser (DK) and Hans Reichenbach (Mxx)
were collected from a variety of soil habitats and stored frozen
or lyophilized immediately after pure cultures were obtained.
In contrast, strain DK1622 has been used as a model for genetic studies by many laboratories in recent decades and has
undergone at least several passages (exact number unknown)
of subculturing after its isolation prior to being obtained by
G.J.V. With one exception, all the isolates and DK1622 are
known to be genotypically distinct from one another within
at least 1 of 2 genes for which sequence data has been obtained (pilA, Wu and Kaiser 1995; csgA, Shimkets et al. 1983;
data not shown). Isolates Mxx17 and Mxx 23 (both isolated
from Minneapolis) show identical sequences for these 2 genes
and therefore may represent the same genotype (although
the isolates may vary at other loci).
Development assay
All development assays were performed in 3 temporally independent blocks with 2 within-block replicates for each genotype–
density combination. Agar plates were incubated at 32 C,
90% relative humidity, and liquid cultures were grown at
32 C, 300 rpm. Isolates were inoculated onto casitone-tris
(CTT) 1.5% agar plates (Hodgkin 1977), grown for 5 days,
transferred into CTT liquid, and kept in exponential-phase
growth for 2 additional days. Culture biovolume densities
(lm3 biomass/ml ’ cells/ml) were determined with a MultisizerTM3 Coulter counter (Beckman-Coulter, Fullerton, CA)
and cultures were centrifuged at 4500 3 g, 22 C for 15
min. Pellets were resuspended in tris/MgSO4/KH2PO4
(TPM) liquid (Kroos et al. 1986) to obtain the highest density
treatment in a given experiment. Lower densities were
obtained by serial dilution with TPM liquid. Resuspended
and diluted samples were spotted on the TPM starvation agar
plates (1.5% agar) in 100-ll aliquots, allowed to dry uncovered
at room temperature, and then incubated.
Sporulation assay
Developmental plates were incubated for 5 days, after which
cell populations were harvested with a scalpel blade, transferred into 0.5 ml double-distilled H2O, and heated at 50 C
for 2 h to select for viable spores. Samples were then sonicated
by microtip and dilution plated into CTT soft agar (0.5%
agar). Plates were incubated for 5 days before colonies were
counted. Sporulation efficiency was calculated as the fraction
of the initial development population that survived as heatand sonication-resistant spores.
RESULTS
Phenotypic variation
Natural isolates of M. xanthus show considerable variation in
fruiting body population phenotypes as a function of density
(Figure 1). For example, isolates Mxx17, DK1622, and Mxx38
all form darkened fruiting body structures at a spotting density of 109 cells/ml. (Darkened interiors indicate that fruiting
bodies contain mature spores.) At 3 3 108 cells/ml, Mxx17 is
unable to form fruiting bodies, whereas DK1622 and Mxx38
form robust fruiting bodies at the same density. At 108 cells/ml,
only Mxx38 is capable of fruiting body construction, whereas
Mxx17 and DK1622 show no visible morphological change.
Kadam and Velicer • Density-dependent survival in social bacteria
Figure 1
Starving population phenotypes of 3 isolates at 3 low cell densities at
153 magnification.
835
Figure 2
Log-transformed sporulation efficiencies (spores produced/initial
population size) of 9 isolates at 5 cell densities. Solid lines are used
for isolates that sporulate efficiently at 3 3 108 cells/ml (isolate
symbols are dash for Mxx38, filled circle for Mxx12, asterisk for
DK836, and filled square for Mxx143), whereas dashed lines indicate
isolates that sporulate poorly at this density (dash for Mxx17, plus
symbol for Mxx15, times symbol for DK1622, delta symbol for
Mxx144, and diamond for Mxx23). Data points show the grand
mean of all 3 replicate estimates (also in Figures 4 and 5), and error
bars indicate 95% confidence intervals about the mean (also in
Figures 3–5).
Variation in sporulation efficiency
Figure 2 shows the sporulation efficiencies of all 9 isolates at
5 initial cell densities (1010, 3 3 109, 109, 3 3 108, and 108 cells/ml)
(Figure 2). Each data point shows the mean value for each
genotype-density treatment across all 3 experimental blocks.
These isolates vary in their patterns of sporulation efficiency
as a function of cell density. Sporulation rates are relatively
similar at the highest density of 1010 cells/ml, covering an
;10-fold range. The variance among isolate sporulation efficiencies, however, increases with each stepwise decrease in
initial cell density (Figure 3). The average slope of the
variance plotted against density across all 3 experimental
blocks is significantly negative (0.98, 1-sample t-test, 1-tailed
P , 0.018). In a 2-factor analysis of variance, genotype,
density, and genotype 3 density interaction all contributed
significantly to the overall observed variation (Table 1).
All isolates but 2 (Mxx17 and Mxx143) appear to be slightly
more efficient at 3 3 109 than at 1010 cells/ml. Below 3 3 109
cells/ml, the isolate patterns separate into 2 visually distinct
sets. One set of 5 isolates (Mxx15, Mxx17, Mxx23, Mxx144, and
DK1622) drop rapidly to low efficiency at 3 3 108 cells/ml. The
second sets of 4 isolates (Mxx12, Mxx38, Mxx143, and DK836)
retain efficiencies at 3 3 108 cells/ml similar to or greater than
their corresponding efficiencies at 1010 cells/ml. These set
groupings are maintained qualitatively at the lowest density
of 108 cells/ml, but the variance within both sets increases
substantially at this lowest density.
All isolates except Mxx38 exhibit the Allee effect over at
least a portion of the density range examined in Figure 3.
DK836 shows the least variance in sporulation efficiency over
the entire density range. Mxx143 shows a pattern similar to
that of DK836 over most densities, but its efficiency drops
much more than that of DK836 at the lowest density. Mxx12
exhibits the highest developmental performance at the intermediate densities of 109 and 3 3 109 cells/ml, but its relative performance drops below that of other isolates at the
extreme densities. The most intriguing pattern is that of
Mxx38, which does not exhibit the Allee effect over this density range, but rather its efficiency actually increases as a function of decreasing density.
In a subsequent experiment, we tested whether Mxx38 is
subject to the Allee effect at densities lower than 108 cells/ml.
Below this level, Mxx38 efficiency dropped precipitously, with
Figure 3
Average within-block variance of log-transformed sporulation
efficiencies for all isolates as a function of cell density.
Behavioral Ecology
836
Table 1
Density and Isolate Contributions to Variation in Sporulation
Estimates
Source of
variation
SS
df
MS
F
P value
Density
Isolate
Interaction
Within
Total
70.45
52.80
29.52
20.69
173.45
4.00
8.00
32.00
90.00
134.00
17.61
6.60
0.92
0.23
76.60
28.71
4.01
3.78 3 10ÿ28
1.12 3 10ÿ21
1.12 3 10ÿ7
df, degrees of freedom; SS, sum-of-squares; MS, mean square.
very few spores detected at 107 cells/ml and zero spores produced at lower densities (at the lower limit of detection, data
for densities below 107 cells/ml not shown) (Figure 4). Thus,
Mxx38 is capable of unusually high rates of spore production
at densities at which all other tested isolates perform poorly,
but Mxx38 does exhibit an Allee pattern at extremely low
densities (107–108 cells/ml).
Also of particular interest were the 2 isolates (Mxx17 and
Mxx143) that did not suffer a decrease in developmental
efficiency at 1010 cells/ml relative to the next highest density
of 3 3 109 cells/ml. We therefore examined the performance
of these isolates at 2 additional higher densities (3 3 1010 and
1011 cells/ml). Intriguingly, Mxx17 suffered only a very slight
decrease in efficiency at these higher densities, whereas
Mxx143 was ;25-fold less efficient at 1011 than at 1010 cells/ml
(Figure 5). This result demonstrates variation among our isolates in density versus performance patterns at extremely high
densities as well as under low-density conditions.
DISCUSSION
We have demonstrated large variation in the effect of population density on survival rate during starvation in a bacterium
that engages in a highly cooperative behavioral program in
response to extreme resource stress. Among the 9 M. xanthus
isolates examined here, variation in sporulation efficiency is
greatest at low population densities, diminishes as population
density increases to standard intermediate laboratory levels,
Figure 4
Sporulation efficiencies of isolate Mxx38 at low cell densities.
Figure 5
Sporulation efficiencies of isolates Mxx17 (solid line) and Mxx 143
(dashed line) at high cell densities.
and then appears to increase again at extremely high population densities. The isolates represent 2 general phenotypic
groups, one of which exhibits much higher sporulation levels
than the other group at low densities. Although all isolates
exhibit the Allee effect at sufficiently low densities, one isolate
of particular interest (Mxx38) actually shows increased survival rate as a function of decreasing density over a range of
densities over which all other isolates exhibit the Allee effect.
Because the selection histories of our isolates’ ancestral lineages are not known, we can only hypothesize that the intraspecific Allee effect variation documented here may be the
result of different selective forces acting on these lineages.
Plausible scenarios consistent with this hypothesis, however,
can readily be generated. In particular, isolates that perform
well under low-density conditions (e.g., Mxx38 and DK836,
Figure 2) may have evolutionary histories in which cooperative performance at low density was more important for fitness
than was such performance during the histories of other isolates that only cooperate well at relatively high densities. Alternatively, isolates that perform particularly well at very high
densities (e.g., Mxx17, Figure 4) may have undergone stronger selection under such conditions than other isolates.
We are unaware of any studies that have sought to quantify
variation in Allee effect patterns among different populations
within any cooperative metazoan species, such as lions, coyotes, mongoose, African wild dogs, or meerkats. It is plausible,
however, that populations of such species that have evolved
for long periods under conditions of relatively high population density (perhaps supported by large prey populations)
would perform poorly under low-density conditions compared
with populations for which low-density conditions with few
prey are the selective norm. Hypotheses about how selection
under high- versus low-density conditions could affect Allee
patterns might be tested directly in laboratory evolution experiments with bacteria such as M. xanthus where only a single
parameter (population density) is varied between distinct evolutionary treatments. Such selection might broaden the range
of densities at which evolved genotypes perform a social function efficiently or might result in trade-offs between performances across the high- versus low-density treatments. More
foundationally, the present study documents the existence of
Kadam and Velicer • Density-dependent survival in social bacteria
genetically based intraspecific variation in Allee effect patterns
on which natural selection could potentially act.
The existence of ‘‘public goods’’ (such as intercellular signals) during M. xanthus development creates the potential
for exploitation among strains in mixed cultures (Velicer
et al. 2000; Velicer 2003). Two forms of social exploitation—
obligate cheating and facultative exploitation—have readily
been detected among laboratory strains and natural isolates,
respectively (Velicer et al. 2000; Fiegna and Velicer 2005). The
large differences in sporulation ability at very low densities
among the strains examined here raise the possibility of a
density-dependent form of cheating. In particular, strains unable
to sporulate at very low densities in clonal isolation might
receive a boost of extracellular complementation by the immediate presence of a strain proficient at low-density development. In principle, such social rescue might be of larger effect
than mere partial complementation and thus result in an
actual fitness advantage for a strain defective at low densities
when it is present at low frequency in a mixed population.
More generally, our results suggest that cell density may play
an important role in determining not only the relative developmental productivity of distinct clonal groups in nature but
also the relative performance of and exploitative relationships
among distinct strains that happen to mix in nature (if such
mixing in fact occurs).
Studying the dynamics of cooperation in bacterial species
such as M. xanthus has several advantages over more complex,
eukaryotic cooperative species. For example, identifying the
genotypic basis of social phenotypes is a simpler affair (although still quite complex) in bacteria than in lions. Many
genes that underlie M. xanthus social development have already been characterized, and a relatively complete picture
of the genetic architecture of M. xanthus sociality will emerge
in the near future as classical genetic studies are joined by
comprehensive genomic and proteomic analyses.
The initial response of M. xanthus populations to resource
deprivation involves a stress-response gene, relA, shared with
many other bacterial species. On starvation, relA induces synthesis of the stress-response signal ((p)ppGpp), which inhibits
synthesis of ribosomes, DNA, and phospholipids when present
at high concentrations (Harris et al. 1998). In M. xanthus,
unlike other bacteria, this stress response is shunted into
a chemical signaling pathway that initiates multicellular
development. In particular, high levels of (p)ppGpp initiate
the production of a quorum-sensing signal known as the
A-signal (Kaplan and Plamann 1996), which, when present
at sufficiently high concentrations, causes large numbers of
individuals to aggregate at high-density loci. The A-signal also
triggers a cascade of subsequent chemical signals that guide
populations through the complete process of development
(Kaiser 2004).
Myxococcus xanthus genotypes that perform well at social development under low-density conditions (e.g., Mxx38) might
do so by 1) responding to a lower minimum concentration of
A-signal, 2) producing greater quantities of A-signal per cell
than do populations that sporulate well only at higher population densities, or 3) aggregating more efficiently at low density in response to a given amount of A-signal. In our study,
one isolate (Mxx38) sporulated with maximum efficiency at
a density 30-fold lower than the density required for maximum efficiency in the standard laboratory isolate (DK1622)
and several other isolates. Under such conditions of nutrient
stress, it seems unlikely that Mxx38 cells would incur the cost
of producing 30-fold more A-signal per cell than their intraspecific counterparts. Thus, we consider heightened sensitivity
to low concentrations of A-signal by Mxx38 and similar isolates
to be more plausible than enhanced A-signal production.
At high densities at which fruiting body formation can be
837
observed for all isolates, isolates that perform well at low density do not appear to aggregate into fruiting bodies faster than
strains the perform well only at high density (SV Kadam, unpublished data), suggesting that superior low-density performance is not due to a general superiority in aggregation rate.
Regardless of its underlying molecular mechanisms, the
great variation in Allee effect patterns among natural isolates
of M. xanthus is likely to affect social performance among
these isolates across soil habitats that vary significantly in
resource levels. The high frequency at which such variation
occurs within a small sample of isolates from one microbial
species suggests that similar patterns are likely to occur among
distinct intraspecific populations of social animals and other
social microbes that vary significantly in their selective histories. Our results also highlight the utility of microbial systems
for addressing ideas and hypotheses in behavioral ecology that
have until recently been applied primarily or exclusively to
higher eukaryotes.
We thank Candice Landry for generating pilot data that helped with
the design of these experiments and anonymous reviewers for helpful
comments on the manuscript.
REFERENCES
Allee WC, Emerson AE, Park O, Park T, Schmidt KP. 1949. Principles
of animal ecology. Philadelphia, PA: Saunders. 837 p.
Bekoff M. 1982. Behavioural ecology of coyotes: social organization,
rearing patterns, space use, and resource defense. Z Tierpsychol
60:281–305.
Courchamp F, Clutton-Brock T, Grenfell B. 1999. Inverse density
dependence and the Allee effect. Trends Ecol Evol 14:405–10.
Courchamp F, Grenfell B, Clutton-Brock T. 1999. Population dynamics of obligate cooperators. Proc R Soc Lond B Biol Sci 266:557–63.
Courchamp F, Macdonald D. 2001. Crucial importance of pack size in
the African wild dog Lycaon pictus. Anim Conserv 4:169–74.
Crespi BJ. 2001. The evolution of social behaviour in microorganisms.
Trends Ecol Evol 16:178–83.
Cui S, Meng J, Bhagwat A. 2001. Availability of glutamate and arginine
during acid challenge determines cell density-dependent survival
phenotype of Escherichia coli strains. Appl Environ Microbiol 67:
4914–8.
Cvitkovitch D, Liu Y, Ellen R. 2003. Quorum sensing and biofilm
formation in Streptococcal infections. J Clin Invest 112:1626–32.
Davis H, Taylor C, Civille J, Strong D. 2004. An Allee effect at the front
of a plant invasion: Spartina in a Pacific estuary. J Ecol 92:321–7.
Dworkin M, Kaiser D. 1985. Cell interactions in myxobacterial growth
and development. Science 230:18–24.
Fiegna F, Velicer GJ. 2005. Exploitative and hierarchical antagonism in
a cooperative bacterium. PLoS Biol 3:1980–7.
Foster J. 1995. Low pH adaptation and the acid tolerance response of
Salmonella typhimurium. Crit Rev Microbiol 21:215–37.
Foster J, Hall H. 1991. Inducible pH homeostasis and the acid tolerance response of Salmonella typhimurium. J Bacteriol 173:5129–35.
Guo PZ, Mueller LD, Ayala FJ. 1991. Evolution of behavior by densitydependent natural selection. Proc Natl Acad Sci USA 88:10905–6.
Harris BZ, Kaiser D, Singer M. 1998. The guanosine nucleotide
(p)ppGpp initiates development and A-factor production in Myxococcus xanthus. Genes Dev 12:1022–35.
Ji G, Beavis RC, Novick RP. 1995. Cell density control of staphylococcal
virulence mediated by an octapeptide pheromone. Proc Natl Acad
Sci USA 92:12055–9.
Kaiser D. 1979. Social gliding is correlated with the presence of pili in
Myxococcus xanthus. Proc Natl Acad Sci USA 76:5952–6.
Kaiser D. 1996. Bacteria also vote. Science 272:1598–9.
Kaiser D. 2004. Signaling in myxobacteria. Annu Rev Microbiol 58:
75–98.
Kaplan HB, Plamann L. 1996. A Myxococcus xanthus cell densitysensing system required for multicellular development. FEMS
Microbiol Lett 139:89–95.
Kim SK, Kaiser D. 1990. Cell motility is required for the transmission of C-factor, an intercellular signal that co-ordinates fruiting
838
body morphogenesis of Myxococcus xanthus. Genes Dev 4:896–
904.
Kroos L, Kuspa A, Kaiser D. 1986. A global analysis of developmentally regulated genes in Myxococcus xanthus. Dev Biol 117:252–66.
Li Y, Hanna M, Svensater G, Ellen R, Cvitkovitch D. 2001. Cell density
modulates acid adaptation in Streptococcus mutans: implications for
survival in biofilms. J Bacteriol 183:6875–84.
Packer C, Herbst L, Pusey AE, Bygott JD, Hanby JP, Cairns SJ, Borgerhoff
Mulder M. 1988. Reproductive success of lions. In: Clutton-Brock TH,
editor. Reproductive success, studies of individual variation in
contrasting breeding systems. Chicago: University of Chicago
Press. p 363–83.
Rietdorf J, Siegert F, Weijer C. 1996. Analysis of optical density wave
propagation and cell movement during mound formation in
Dictyostelium discoideum. Dev Biol 177:427–38.
Rosenbluh A, Nir R, Sahar E, Rosenberg E. 1989. Cell-density dependent lysis and sporulation of Myxococcus xanthus in agarose
microbeads. J Bacteriol 171:4923–9.
Shimkets LJ. 1999. Intercellular signaling during fruiting-body
development of Myxococcus xanthus. Annu Rev Microbiol 53:525–49.
Shimkets LJ, Gill RE, Kaiser D. 1983. Developmental interaction in
Myxococcus xanthus and the spoC locus. Proc Natl Acad Sci USA
80:1406–10.
Singer M, Kaiser D. 1995. Ectopic production of guanosine penta- and
tetraphosphate can initiate early developmental gene expression in
Myxococcus xanthus. Genes Dev 9:1633–44.
Behavioral Ecology
Stephens PA, Sutherland WJ. 1999. Consequences of the Allee effect
for behaviour, ecology and conservation. Trends Ecol Evol 14:401–5.
Stephens PA, Sutherland WJ, Freckleton RP. 1999. What is the Allee
effect? Oikos 87:185–90.
Thorne SH, Williams HD. 1999. Cell density-dependent starvation
survival of Rhizobium leguminosarum bv phaseoli: identification of
the role of an N-acyl homoserine lactone in adaptation to stationaryphase survival. J Bacteriol 181:981–90.
vanOss C, Panfilov A, Hogeweg P, Siegert F, Weijer C. 1996. Spatial
pattern formation during aggregation of the slime mould Dictyostelium discoideum. J Theor Biol 181:203–13.
Velicer GJ. 2003. Social strife in the microbial world. Trends Microbiol
11:330–7.
Velicer GJ, Kroos L, Lenski RE. 2000. Developmental cheating in the
social bacterium Myxococcus xanthus. Nature 404:598–601.
Wilson K, Thomas MB, Blanford S, Doggett M, Simpson SJ, Moore SL.
2002. Coping with crowds: density-dependent disease resistance in
desert locusts. Proc Natl Acad Sci USA 99:5471–5.
Wu SS, Kaiser D. 1995. Genetic and functional evidence that Type IV
pili are required for social gliding motility in Myxococcus xanthus.
Mol Microbiol 18:547–58.
Zahavi A, Ralt D. 1984. Social adaptation in myxobacteria. In:
Rosenberg E, editor. Myxobacteria: development and cell interactions. New York: Springer-Verlag. p 215–20.
Zusman D. 1984. Cell-cell interactions and development in Myxococcus
xanthus. Q Rev Biol 59:119–38.